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Myeloproliferative disorder refers to a group of slow-growing blood cancers in which large numbers of abnormal red blood cells, white blood cells, or platelets grow in the bone marrow and blood. Learn about myeloproliferative disorders and find information on how we support and care for people with myeloproliferative disorders before, during, and after treatment.
The Hematologic Oncology Center provides specialized care for all types of cancers of the blood, including leukemia, lymphoma, multiple myeloma and Waldenström’s macroglobulinemia.
The center also includes the hematopoietic stem cell transplantation program, which is one of the largest and most experienced in the world.
To make sure your care is as seamless as possible, a dedicated team of clinicians, who are highly specialized experts in your type of blood cancer, will care for you throughout the treatment process, from diagnosis though long-term follow-up.
Your care team will include oncologists, surgeons, hematologists, physician assistants, nurses, and clinical social workers who are committed to delivering safe, high-quality patient care.
We develop personalized, comprehensive treatment plans for all our patients, offering the latest therapies and supportive resources and taking your individual needs into account.
In addition to conventional treatment approaches, you may have the opportunity to participate in clinical trials that offer access to new, innovative treatments for your type of cancer.
A variety of services and programs also support your care, including nutrition services, emotional support and counseling, pain management, donor services for stem cell transplantation, and support for cancer survivors.
Learn more about treatment and care in the Hematologic Oncology Center
New patients: See Center page for phone numbers by treatment program
All other inquiries: 617-632-6140
Myelodysplastic/myeloproliferative diseases are diseases of the blood and bone marrow. Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. The lymphoid stem cell develops into a white blood cell. The myeloid stem cell develops into one of three types of mature blood cells:
In myelodysplastic diseases, the blood stem cells do not mature into healthy red blood cells, white blood cells, or platelets. The immature blood cells, called blasts, do not work the way they should and die in the bone marrow or soon after they enter the blood. As a result, there are fewer healthy red blood cells, white blood cells, and platelets.
In myeloproliferative diseases, a greater than normal number of blood stem cells develop into one or more types of blood cells and the total number of blood cells slowly increases.
This summary is about diseases that have features of both myelodysplastic and myeloproliferative diseases. See the following PDQ summaries for more information about related diseases:
The 3 main types of myelodysplastic/myeloproliferative disease include the following:
When a myelodysplastic/myeloproliferative disease does not match any of these types, it is called myelodysplastic/myeloproliferative disease, unclassifiable (MDS/MPD-UC).
Myelodysplastic/myeloproliferative diseases may progress to acute leukemia.
The following tests and procedures may be used:
In CMML, the body tells too many bloodstem cells to develop into two types of white blood cells called myelocytes and monocytes. Some of these blood stem cells never become mature white blood cells. These immature white blood cells are called blasts. Over time, the myelocytes, monocytes, and blasts crowd out the red blood cells and platelets in the bone marrow. When this happens, infection, anemia, or easy bleeding may occur.
Anything that increases your chance of getting a disease is called a risk factor. Possible risk factors for CMML include the following:
These and other symptoms may be caused by CMML. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
The prognosis (chance of recovery) and treatment options for CMML depend on the following:
Juvenile myelomonocytic leukemia is a rare childhood cancer that occurs more often in children younger than 2 years. Children who have neurofibromatosis type 1 and males have an increased risk of developing juvenile myelomonocytic leukemia.
In JMML, the body tells too many bloodstem cells to develop into two types of white blood cells called myelocytes and monocytes. Some of these blood stem cells never become mature white blood cells. These immature white blood cells are called blasts. Over time, the myelocytes, monocytes, and blasts crowd out the red blood cells and platelets in the bone marrow. When this happens, infection, anemia, or easy bleeding may occur.
These and other symptoms may be caused by JMML. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
The prognosis (chance of recovery) and treatment options for JMML depend on the following:
In atypical chronic myelogenous leukemia (aCML), the body tells too many bloodstem cells to develop into a type of white blood cell called granulocytes. Some of these blood stem cells never become mature white blood cells. These immature white blood cells are called blasts. Over time, the granulocytes and blasts crowd out the red blood cells and platelets in the bone marrow.
The leukemiacells in aCML and chronic myelogenous leukemia (CML) look alike under a microscope. However, in aCML a certain chromosome change, called the "Philadelphia chromosome" is not present.
These and other symptoms may be caused by aCML. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
The prognosis (chance of recovery) for aCML depends on the number of red blood cells and platelets in the blood.
In myelodysplastic/myeloproliferative disease, unclassifiable (MDS/MPD-UC), the body tells too many bloodstem cells to develop into red blood cells, white blood cells, or platelets. Some of these blood stem cells never become mature blood cells. These immature blood cells are called blasts. Over time, the abnormal blood cells and blasts in the bone marrow crowd out the healthy red blood cells, white blood cells, and platelets.
MDS/MPD-UC is a very rare disease. Because it is so rare, the factors that affect risk and prognosis are not known.
These and other symptoms may be caused by MDS/MPD-UC. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
Staging is the process used to find out how far the cancer has spread. There is no standard staging system for myelodysplastic/myeloproliferative diseases. Treatment is based on the type of myelodysplastic/myeloproliferative disease the patient has. It is important to know the type in order to plan treatment.
When cancer cells spread outside the blood, a solid tumor may form. This process is called metastasis. The three ways that cancer cells spread in the body are:
The new (metastatic) tumor is the same type of cancer as the primary cancer. For example, if leukemia cells spread to the brain, the cancer cells in the brain are actually leukemia cells. The disease is metastatic leukemia, not brain cancer.
Different types of treatments are available for patients with myelodysplastic/myeloproliferative diseases. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated. Combination chemotherapy is treatment using more than one anticancer drug.
13-cis retinoic acid is a vitamin-like drug that slows the cancer's ability to make more cancer cells and changes the way these cells look and act.
Stem cell transplant is a method of replacing blood-forming cells that are destroyed by chemotherapy. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Supportive care is given to lessen the problems caused by the disease or its treatment. Supportive care may include transfusiontherapy or drug therapy, such as antibiotics to fight infection.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
Targeted therapy is a cancer treatment that uses drugs or other substances to attack cancer cells without harming normal cells. Farnesyltransferase inhibitors are one type of targeted therapy that is being studied in the treatment of JMML.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Treatment of chronic myelomonocytic leukemia (CMML) may include the following:
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with chronic myelomonocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Treatment of juvenile myelomonocytic leukemia (JMML) may include the following:
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with juvenile myelomonocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Treatment of atypical chronic myelogenous leukemia (aCML) may include chemotherapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with atypical chronic myeloid leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Because myelodysplastic/myeloproliferative disease, unclassifiable (MDS/MPD-UC) is a rare disease, little is known about its treatment. Supportive care treatments are used to manage problems caused by the disease such as infection, bleeding, and anemia.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with myelodysplastic/myeloproliferative disease, unclassifiable. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
For more information from the National Cancer Institute about myelodysplastic/myeloproliferative diseases, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on August 1, 2008.
The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either myelodysplastic syndromes (MDS) or chronic myeloproliferative disorders (CMPD). This category is composed of three major myeloid disorders: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myeloid leukemia (aCML). Myeloid disease that shows features of both MDS and CMPD but does not meet the criteria for any of the three major MDS/MPN entities is designated as myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC).
The French-American-British classification scheme for myeloid disorders did not contain this overlap category, which made the classification of CMML particularly difficult. Recognizing the special diagnostic challenge that these diseases represent, a group of pathologists and clinicians sponsored by the World Health Organization (WHO) created the MDS/MPN category to provide a less restrictive view of myeloid disorders, which in some instances clearly overlap. The WHO group proposed that the new MDS/MPN category would allow for more focused clinical and laboratory investigations of myeloid proliferation, abnormal proliferation, and dysplasia.
The etiology of MDS/ MPN is not known. The incidence of MDS/MPN varies widely, ranging from approximately 3 per 100,000 individuals older than 60 years annually for CMML to as few as 0.13 per 100,000 children from birth to 14 years annually for JMML. Reliable data concerning the incidence of aCML, a recently defined entity, are not available. The incidence of MDS/MPN-UC is unknown.
The pathophysiology of MDS/MPN involves abnormalities in the regulation of myeloid pathways for cellular proliferation, maturation, and survival. Clinical symptoms are caused by complications resulting from the following:
Patients with MDS/MPN do not have a Philadelphia chromosome or BCR/ABL fusion gene. No specific genetic defects have been identified for any of these entities, though abnormalities in regulation of the ras pathway of signaling proteins appears to be a common finding in CMML, aCML, and JMML and may have some role in the abnormal myeloid proliferation associated with these diseases. In general, treatment of these diseases is tailored to the manifestations, myeloproliferative or myelodysplastic, that predominate in the individual patient.
Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100 (7): 2292-302, 2002.
Germing U, Gattermann N, Minning H, et al.: Problems in the classification of CMML--dysplastic versus proliferative type. Leuk Res 22 (10): 871-8, 1998.
Voglová J, Chrobák L, Neuwirtová R, et al.: Myelodysplastic and myeloproliferative type of chronic myelomonocytic leukemia--distinct subgroups or two stages of the same disease? Leuk Res 25 (6): 493-9, 2001.
Vardiman JW: Myelodysplastic/myeloproliferative diseases: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 47-8.
Bain BJ: The relationship between the myelodysplastic syndromes and the myeloproliferative disorders. Leuk Lymphoma 34 (5-6): 443-9, 1999.
Note: Chronic myelomonocytic leukemia (CMML) was classified as a myelodysplastic syndrome (MDS) under the French-American-British scheme. The World Health Organization classification removed CMML from MDS, placing it in the new category Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN).
CMML is a clonal disorder of a bone marrow stem cell. Monocytosis is a major defining feature. CMML exhibits heterogenous clinical, hematological, and morphologic features, varying from predominantly myelodysplastic to predominantly myeloproliferative.
CMML is characterized pathologically by the following:
Clinical features of CMML include the following:
The median age at diagnosis of CMML is 65 to 75 years with a male predominance of 1.5 to 3.1. Because CMML is grouped with chronic myeloid leukemia in some epidemiologic surveys and with MDS in others, no reliable incidence data are available for CMML. Although the specific etiology of CMML is unknown, exposure to occupational and environmental carcinogens, ionizing radiation, and cytotoxic agents has been associated in some cases.
Morphologically, the disease is characterized by a persistent peripheral blood monocytosis (always >1 × 109/L) that may exceed 80 × 109/L with monocytes typically accounting for more than 10% of the white blood cells. Monocytes, though typically mature with an unremarkable morphology, can exhibit abnormal granulation, unusual nuclear lobation, or finely dispersed nuclear chromatin. Fewer than 20% blasts are seen in the blood or bone marrow. Neutrophilia occurs in nearly 50% of patients with neutrophil precursors (e.g., promyelocytes and myelocytes) accounting for more than 10% of the white blood cells. Mild normocytic anemia is common. (Refer to the PDQ summary on Fatigue for more information on anemia.) Moderate thrombocytopenia is often present. Bone marrow findings include the following:
Hepatosplenomegaly may be present. Autoimmune phenomena, including pyoderma gangrenosum, vasculitis, and idiopathic thrombocytopenia have been observed in CMML. Care should be taken to identify cases of CMML with eosinophilia, a subtype of CMML, because of its association with severe tissue damage secondary to eosinophil degranulation. In CMML with eosinophilia, all criteria for CMML are present, and the eosinophil count in the peripheral blood is more than 1.5 × 109.
Although clonal cytogenetic abnormalities are found in 20% to 40% of patients with CMML, none is specific. Point mutations of ras genes may occur in as many as 40% of patients with CMML. The median survival time for CMML is 12 to 24 months. Prognostic factors associated with shorter survival include the following:
Progression to acute leukemia occurs in approximately 15% to 20% of cases.
Various chemotherapy regimens for CMML have been used with only modest success. In a study evaluating single-agent therapy with topotecan, a topoisomerase I inhibitor, 25 patients with CMML were treated with topotecan at doses that induce bone marrow aplasia (2.0 mg/m2/day by continuous infusion for 5 days). Complete hematologic remissions were induced in 28% of patients. Toxic effects were significant, and the median duration of remission was 8 months.[Level of evidence: 3iiiDiv] In a follow-up study, topotecan was used in combination with cytarabine, a pyrimidine-analog antimetabolite. This combination regimen induced complete remission in 44% of patients with CMML; median duration of complete response was 50 weeks, and patients required monthly maintenance therapy.[Level of evidence: 3iiiDiv]
Treatment with hydroxyurea is an option. In a randomized clinical trial, 105 patients with advanced CMML were enrolled to compare treatment with hydroxyurea versus treatment with etoposide. Doses were scheduled to escalate to hydroxyurea 4 g/d and etoposide 600 mg/week in the absence of response and finally to adjust to maintain white blood cells between 5 × 109/L and 10 × 109/L. Median actuarial survival was 20 months in the hydroxyurea arm versus 9 months in the etoposide arm (P < .001). Main factors associated with poor survival were allocation to the etoposide arm, unfavorable karyotype (i.e., monosomy 7 or complex abnormalities), and anemia.[Level of evidence: 1iiA]
The nucleoside 5-azacitidine is an inhibitor of DNA methyltransferase that has been approved for the treatment of MDS, largely based on a Cancer and Leukemia Group B randomized trial. This trial, in which patients were randomized to supportive care versus 5-azacitidine (75 mg/m2/day subcutaneously for 7 days every 28 days), included 10 patients with CMML.[Level of evidence: 1iiDii]
Bone marrow transplantation (BMT) or stem cell transplantation appears to be the only current treatment that alters the natural history of CMML. In a review of 118 young MDS patients (median age 24, age range 0.3–53 years) who received allogeneic BMT from matched unrelated donors, the actuarial probability of survival at 2 years for the 12 patients with CMML was 10%. Transplant-related mortality was influenced by the age of the patient (i.e., <18 years, 40%; 18–35 years, 61%; >35 years, 81%). This study included patients who received transplants as early as 1986, which may have influenced the patient survival data.[Level of evidence: 3iiiA] In a recent review of 50 allogeneic transplantations for CMML (i.e., median age 44, age range 19–61 years) from related (n = 43) or unrelated (n = 7) donors, the 5-year-estimated overall survival was 21%. The 5-year estimated probability of relapse was 49%. The data showed a trend for a lower relapse probability of acute graft versus host disease grade II through grade IV and for a higher relapse rate in patients with T cell-depleted grafts, suggesting a graft-versus-CMML effect. This latter series represents the largest cohort of patients with adult CMML and allogeneic stem cell transplantation to date.[Level of evidence: 3iiiA]
A case report suggests that targeted therapy with imatinib mesylate may be effective in a subset of patients with CMML related to PDGFβR fusion oncogenes.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with chronic myelomonocytic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.
Orazi A, Germing U: The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia 22 (7): 1308-19, 2008.
Onida F, Beran M: Chronic myelomonocytic leukemia: myeloproliferative variant. Curr Hematol Rep 3 (3): 218-26, 2004.
Emanuel PD: Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Leukemia 22 (7): 1335-42, 2008.
Aul C, Bowen DT, Yoshida Y: Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. Haematologica 83 (1): 71-86, 1998.
Kouides PA, Bennett JM: Morphology and classification of the myelodysplastic syndromes and their pathologic variants. Semin Hematol 33 (2): 95-110, 1996.
Bennett JM, Catovsky D, Daniel MT, et al.: The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol 87 (4): 746-54, 1994.
Michaux JL, Martiat P: Chronic myelomonocytic leukaemia (CMML)--a myelodysplastic or myeloproliferative syndrome? Leuk Lymphoma 9 (1-2): 35-41, 1993.
Maschek H, Georgii A, Kaloutsi V, et al.: Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients. Eur J Haematol 48 (4): 208-14, 1992.
Saif MW, Hopkins JL, Gore SD: Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 43 (11): 2083-92, 2002.
Nösslinger T, Reisner R, Grüner H, et al.: Dysplastic versus proliferative CMML--a retrospective analysis of 91 patients from a single institution. Leuk Res 25 (9): 741-7, 2001.
Onida F, Kantarjian HM, Smith TL, et al.: Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood 99 (3): 840-9, 2002.
Bennett JM: Chronic myelomonocytic leukemia. Curr Treat Options Oncol 3 (3): 221-3, 2002.
Germing U, Kündgen A, Gattermann N: Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma 45 (7): 1311-8, 2004.
Beran M, Kantarjian H, O'Brien S, et al.: Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 88 (7): 2473-9, 1996.
Beran M, Estey E, O'Brien S, et al.: Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia. J Clin Oncol 17 (9): 2819-30, 1999.
Wattel E, Guerci A, Hecquet B, et al.: A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Français des Myélodysplasies and European CMML Group. Blood 88 (7): 2480-7, 1996.
Kaminskas E, Farrell A, Abraham S, et al.: Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res 11 (10): 3604-8, 2005.
Arnold R, de Witte T, van Biezen A, et al.: Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group. Bone Marrow Transplant 21 (12): 1213-6, 1998.
Kröger N, Zabelina T, Guardiola P, et al.: Allogeneic stem cell transplantation of adult chronic myelomonocytic leukaemia. A report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 118 (1): 67-73, 2002.
Magnusson MK, Meade KE, Nakamura R, et al.: Activity of STI571 in chronic myelomonocytic leukemia with a platelet-derived growth factor beta receptor fusion oncogene. Blood 100 (3): 1088-91, 2002.
Note: Juvenile myelomonocytic leukemia (JMML) was classified as a myelodysplastic syndrome (MDS) under the French-American-British scheme. The World Health Organization classification removed JMML from MDS, placing it in the new category Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN).
JMML (also known as juvenile chronic myelomonocytic leukemia) is a rare hematopoietic malignancy of childhood accounting for 2% of all childhood leukemias. A number of clinical and laboratory features distinguish JMML from adult-type chronic myeloid leukemia, a disease noted only occasionally in children. In children presenting with clinical features suggestive of JMML, a definitive diagnosis requires the following:
The clinical features of JMML at the time of initial presentation may include the following:
The clinical and laboratory features of JMML can closely mimic a variety of infectious diseases, including the following:
Laboratory testing can distinguish whether JMML or infectious diseases have affected the clinical and hematologic findings.
JMML typically presents in young children (median age approximately 1 year) and occurs more commonly in boys (male to female ratio approximately 2.5:1). The cause for JMML is not known. Children with neurofibromatosis type 1 (NF1) are at increased risk for developing JMML, and up to 14% of cases of JMML occur in children with NF1.
Morphologically, the peripheral blood picture in this disease shows leukocytosis, anemia, and frequently, thrombocytopenia. The median reported white blood cell count varies from 25 × 109/L to 35 × 109/L. In 5% to 10% of children with JMML, however, it is greater than 100 × 109/L. The leukocytosis is comprised of neutrophils, promyelocytes, myelocytes, and monocytes. Blasts, including promonocytes, usually account for less than 5% of the white blood cells and always for less than 20%. Nucleated red blood cells are seen frequently. Thrombocytopenia is typical and may be severe. Bone marrow findings include the following:
A distinctive characteristic of JMML leukemia cells is their spontaneous proliferation in vitro without the addition of exogenous stimuli, an ability that results from the leukemia cells being hypersensitive to GM-CSF. No Philadelphia chromosome or BCR/ABL fusion gene exists. Although cytogenetic abnormalities, including monosomy 7, occur in 30% to 40% of patients, none is specific for JMML. In JMML associated with NF1, loss of the normal NF1 allele is common, and loss of heterozygosity for NF1 has been observed in some patients with JMML who lack the NF1 phenotype. This genetic alteration results in a loss of neurofibromin, a protein that is involved in the regulation of the ras family of oncogenes. Point mutations in ras have been reported to occur in the leukemic cells of 20% of patients with JMML.
The median survival times for JMML vary from approximately 10 months to more than 4 years, depending partly on the type of therapy chosen. Prognosis is related to age at the time of diagnosis. The prognosis is better in children younger than 1 year at the time of diagnosis. Children older than 2 years at the time of diagnosis have a much worse prognosis. A low platelet count and a high Hb F level have been associated with a worse prognosis. Approximately 10% to 20% of cases may evolve to acute leukemia.
No consistently effective therapy is available for JMML. Historically, more than 90% of patients have died despite the use of chemotherapy. Patients appeared to follow three distinct clinical courses:
A recent retrospective review described 60 children with JMML treated with chemotherapy (nonintensive and intensive) and/or bone marrow transplantation (BMT) using sibling or unrelated human leukocyte antigen (HLA)-matched donor marrow or autologous marrow. The median survival was 4.4 years.[Level of evidence: 3iiiA]
BMT seems to offer the best chance of cure for JMML. A summary of the outcome of 91 patients with JMML treated with BMT in 16 different reports is as follows: 38 patients (41%) were still alive at the time of reporting, including 30 of the 60 (50%) patients who received grafts from HLA-matched or 1-antigen mismatched familial donors, 2 of 12 (17%) with mismatched donors, and 6 of 19 (32%) with matched unrelated donors.
In a retrospective study investigating the role of BMT for chronic myelomonocytic leukemia (CMML), 43 children with CMML and given BMT were evaluated. In 25 cases, the donor was a HLA-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 cases a matched unrelated donor. Conditioning regimens consisted of total-body radiation therapy and chemotherapy in 22 patients, whereas busulfan with other cytotoxic drugs were used in the remaining patients. Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. Probabilities of transplant-related mortality for children transplanted from HLA-identical/one-antigen-disparate relatives or from matched unrelated donors/mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%; the 5-year event-free survival (EFS) rate was 31%. The authors of this study concluded that children with CMML and an HLA-compatible relative should be transplanted as early as possible.[Level of evidence: 3iiiDii]
In a more recent retrospective review from Japan, the records of 27 children with JMML who underwent allogeneic hematopoietic stem cell transplantation (SCT) were examined to determine the role of different variables that potentially influence outcome. The source of grafts was HLA-identical siblings in 12 cases, HLA-matched unrelated individuals in 10 cases, and HLA-mismatched donors in five cases. Total-body radiation therapy was used in 18 cases. At 4 years after SCT, EFS and overall survival (OS) were 54.2% (+/- 11.2% standard error [SE]) and 57.9% (+/- 11.0% [SE]), respectively. Six patients died of relapse and three died of complications. Patients with abnormal karyotypes showed a significantly lower OS than those with normal karyotypes (P < .001). Patients younger than 1 year showed a significantly higher OS than those older than 1 year. Other variables studied were not associated with OS. A multivariate analysis of these factors indicated that the abnormal karyotype was the only significant risk factor for lower OS.[Level of evidence: 3iiiA] Five of 10 patients with JMML responded to the oral administration of 13-cis retinoic acid (i.e., two complete responses, three partial responses); median duration of response was 37 months. Treatment with retinoic acid was associated with a decrease in spontaneous colony formation and in GM-CSF hypersensitivity.
Molecular-targeting therapies currently under evaluation include the use of farnesyltransferase inhibitors that prevent ras protein maturation, which may result in increased tumor cell apoptosis and inhibition of tumor cell growth.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with juvenile myelomonocytic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Emanuel PD: Myelodysplasia and myeloproliferative disorders in childhood: an update. Br J Haematol 105 (4): 852-63, 1999.
Hasle H, Niemeyer CM, Chessells JM, et al.: A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 17 (2): 277-82, 2003.
Aricò M, Biondi A, Pui CH: Juvenile myelomonocytic leukemia. Blood 90 (2): 479-88, 1997.
Niemeyer CM, Fenu S, Hasle H, et al.: Response: differentiating myelomonocytic leukemia from infectious disease. Blood 91(1): 365-367.
Vardiman JW, Pierre R, Imbert M, et al.: Juvenile myelomonocytic leukaemia. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 55-7.
Luna-Fineman S, Shannon KM, Atwater SK, et al.: Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients. Blood 93 (2): 459-66, 1999.
Niemeyer CM, Arico M, Basso G, et al.: Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS) Blood 89 (10): 3534-43, 1997.
Lorenzana A, Lyons H, Sawaf H, et al.: Human herpesvirus 6 infection mimicking juvenile myelomonocytic leukemia in an infant. J Pediatr Hematol Oncol 24 (2): 136-41, 2002.
Luna-Fineman S, Shannon KM, Lange BJ: Childhood monosomy 7: epidemiology, biology, and mechanistic implications. Blood 85 (8): 1985-99, 1995.
Pinkel D: Differentiating juvenile myelomonocytic leukemia from infectious disease. Blood 91 (1): 365-7, 1998.
Stiller CA, Chessells JM, Fitchett M: Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study. Br J Cancer 70 (5): 969-72, 1994.
Passmore SJ, Hann IM, Stiller CA, et al.: Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system. Blood 85 (7): 1742-50, 1995.
Hess JL, Zutter MM, Castleberry RP, et al.: Juvenile chronic myelogenous leukemia. Am J Clin Pathol 105 (2): 238-48, 1996.
Emanuel PD, Bates LJ, Castleberry RP, et al.: Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 77 (5): 925-9, 1991.
Emanuel PD, Snyder RC, Wiley T, et al.: Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors. Blood 95 (2): 639-45, 2000.
Side LE, Emanuel PD, Taylor B, et al.: Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 92 (1): 267-72, 1998.
Flotho C, Valcamonica S, Mach-Pascual S, et al.: RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 13 (1): 32-7, 1999.
Locatelli F, Niemeyer C, Angelucci E, et al.: Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood. J Clin Oncol 15 (2): 566-73, 1997.
Freedman MH, Estrov Z, Chan HS: Juvenile chronic myelogenous leukemia. Am J Pediatr Hematol Oncol 10 (3): 261-7, 1988 Fall.
Sanders JE, Buckner CD, Thomas ED, et al.: Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia. Blood 71 (4): 1144-6, 1988.
Smith FO, King R, Nelson G, et al.: Unrelated donor bone marrow transplantation for children with juvenile myelomonocytic leukaemia. Br J Haematol 116 (3): 716-24, 2002.
Manabe A, Okamura J, Yumura-Yagi K, et al.: Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group. Leukemia 16 (4): 645-9, 2002.
Castleberry RP, Emanuel PD, Zuckerman KS, et al.: A pilot study of isotretinoin in the treatment of juvenile chronic myelogenous leukemia. N Engl J Med 331 (25): 1680-4, 1994.
Rowinsky EK, Windle JJ, Von Hoff DD: Ras protein farnesyltransferase: A strategic target for anticancer therapeutic development. J Clin Oncol 17 (11): 3631-52, 1999.
Atypical chronic myelogenous leukemia (aCML) is a leukemic disorder that exhibits both myelodysplastic and myeloproliferative features at the time of diagnosis.
Atypical CML is characterized pathologically by the following:
Clinical features of aCML include the following:
Although cytogenetic abnormalities are found in as many as 80% of the patients with aCML, none is specific. No Philadelphia chromosome or BCR/ABL fusion gene exists.
The exact incidence of aCML is unknown. The median age at the time of diagnosis of this rare leukemic disorder has been reported to be in the seventh or eighth decade of life.
Morphologically, aCML is characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to chronic myelogenous leukemia, but cytogenetically it lacks a Philadelphia chromosome or BCR/ABL fusion gene. The white blood cell count in the peripheral blood is variable. Median values range from 35 × 109/L to 96 × 109/L, and some patients may have white blood cell counts greater than 300 × 109/L. Blasts in the peripheral blood typically account for less than 5% of the white blood cells. Immature neutrophils usually total 10% to 20% or more. The percentage of monocytes is rarely more than 10%. Minimal basophilia may be present. Nuclear abnormalities, such as acquired Pelger-Huët anomaly, may be seen in the neutrophils. Moderate anemia (often showing changes indicative of dyserythropoiesis) and thrombocytopenia are common. Bone marrow findings include the following: 
The median survival times for aCML are reported to be less than 20 months, and thrombocytopenia and marked anemia are poor prognostic factors. Atypical CML evolves to acute leukemia in approximately 25% to 40% of patients. In the remainder, fatal complications include resistant leukocytosis, anemia, thrombocytopenia, hepatosplenomegaly, cerebral bleeding associated with thrombocytopenia, and infection.
The optimal treatment of aCML is uncertain because of the rare incidence of this chronic leukemic disorder. Treatment with hydroxyurea may lead to short-lived partial remissions of 2- to 4-months' duration. Atypical CML, appears to respond poorly to treatment with interferon-alpha.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with atypical chronic myeloid leukemia, BCR-ABL1 negative. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Hernández JM, del Cañizo MC, Cuneo A, et al.: Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia. Ann Oncol 11 (4): 441-4, 2000.
Costello R, Sainty D, Lafage-Pochitaloff M, et al.: Clinical and biological aspects of Philadelphia-negative/BCR-negative chronic myeloid leukemia. Leuk Lymphoma 25 (3-4): 225-32, 1997.
Kurzrock R, Bueso-Ramos CE, Kantarjian H, et al.: BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol 19 (11): 2915-26, 2001.
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/ MPN-UC) (also known as mixed myeloproliferative/ myelodysplastic syndrome, unclassifiable and overlap syndrome, unclassifiable) shows features of both myeloproliferative disease and myelodysplastic disease but does not meet the criteria for any of the other MDS/MPN entities.
Diagnostic criteria for MDS/MPN-UC can be either:
The incidence and etiology of MDS/MPN-UC are unknown.
Laboratory features typically include anemia and dimorphic erythrocytes on the peripheral blood smear. Thrombocytosis (platelet count >600 × 109/L) or leukocytosis (white blood cell count >13 × 109/L) are present. Neutrophils may exhibit dysplastic features, and giant or hypogranular platelets may be present. Blasts make up less than 20% of the white blood cells and of the nucleated cells of the bone marrow. The bone marrow is hypercellular and may exhibit proliferation in any or all of the myeloid lineages. Dysplastic features are present in at least one cell line.
No cytogenetic or molecular findings are available that are specific for MDS/MPN-UC. In one small series, six of nine patients (those with ringed sideroblasts associated with marked thrombocytosis [RARS-T]) showed a JAK2 V617F mutation causing constitutive activation of the JAK2 tyrosine kinase (a mutation also commonly observed in patients with polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis). Because of its rare occurrence, the prognosis and predictive factors are unknown.
Adult patients with MDS/MPN associated with platelet-derived growth factor receptor gene rearrangements are candidates for imatinib mesylate at standard dosages. Because of its rare occurrence, the literature only minimally addresses other treatment options for MDS/MPN-UC. Supportive care involves treating cytopenias and infection as necessary.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with myelodysplastic/myeloproliferative neoplasm, unclassifiable. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Szpurka H, Tiu R, Murugesan G, et al.: Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. Blood 108 (7): 2173-81, 2006.
U.S. Food and Drug Administration: FDA approves imatinib mesylate (Gleevec) as a single agent for the treatment of multiple indications. Rockville, Md: Food and Drug Administration, Center for Drug Evaluation and Research, Office of Oncology Drug Products (OODP), 2006. Available online. Last accessed February 07, 2012.
This information was last updated on April 24, 2014.
Our licensed social workers are here to help adult patients and their loved ones face the many new concerns and anxieties following a cancer diagnosis, offering emotional support and assistance with obtaining needed resources.
If you are dealing with the death of a loved one, grief can be a lonely and isolating experience. The Bereavement Program provides support to bereaved family members and friends following the death of a patient.
Concierge Services is your one-stop place to learn about Dana-Farber programs, services and resources, as well as information on getting around Boston, finding lodging or restaurants, and activities in the area.
The Expressive Arts Therapy program, sponsored by the Leonard P. Zakim Center for Integrative Therapies, provides adult patients, family members, and caregivers with a variety of options to support well-being during cancer treatment. From live music meditation to painting technique workshops, the program offers a range of creative outlets to suit every interest.
Dana-Farber and Brigham and Women's Hospital, including parking facilities, are fully accessible to people with disabilities. There are wheelchairs at the main entrance, and security staff can provide personal assistance. We also have many educational materials available in large print and audiotape formats.
The Ethics Consultation Service is available for patients and families who may be facing difficult decisions and choices regarding care. Our goal is to bring together patients, families and health care providers to talk about ethical concerns and help everyone involved arrive at a resolution that is right for all.
This comprehensive resource offers guidance, information and resources to support the entire family, including how to talk to children about cancer, advice for the well partner, and creating a support network.
Find practical tips and suggestions for individuals caring for a family member or friend with cancer, including creating a caregiving plan, finding community resources, and looking after your own well-being.
Friends' Place provides personal consultations to help cancer patients of all ages cope with changes in physical appearance that result from cancer treatment. Our experienced, compassionate team provides fittings for compression garments or breast prostheses, helps with wigs and other head coverings, and offers make-up and skincare advice.
The Friends' Corner Gift Shop, located on the first floor of the Yawkey Center for Cancer Care, offers a wide selection of unique gifts and everyday items for patients, families and staff.
Dana-Farber offers several services to help you and your family manage the financial side of cancer treatment. From creating bill payment schedules and estate planning advice to debt management and resource assistance for patients in need, our team is here for you.
Every year, thousands of patients with cancer from around the world come to Dana-Farber for their care. We provide a wide array of logistical and other services for individuals who live outside the United States.
Dana-Farber provides interpreting services for patients whose first language is not English. Interpreters may be requested for any activity, including registration, booking appointments, attending treatments and exams, support groups, and meetings with doctors and other members of your health care team.
Our nutritionists are registered dietitians who can assist you in planning an optimal diet during any stage of your cancer journey, cope with any side effects you may experience, and answer your questions about the latest findings on cancer and nutrition.
One-to-One connects adult patients, family members and caregivers with individuals who have gone through cancer themselves, providing an experienced and reassuring perspective for those facing a cancer diagnosis, treatment and recovery.
The Eleanor and Maxwell Blum Patient and Family Resource Center and its satellite resource rooms are staffed by health care professionals and provide computer stations, books, brochures, videos, and CDs to help you find information and support on a variety of issues about cancer treatment and care.
Patients websites help friends and family members stay up-to-date on their loved ones' condition and write messages of support and encouragement.
The Dana-Farber pharmacy fills prescriptions for all pediatric and adult patients. Our pharmacists are an extension of the patient care team and work closely with your physicians to provide seamless, convenient, safe care.
More than 1,200 Dana-Farber patients and their families have enjoyed free trips to baseball games, theater shows, museums, and other attractions this year through the Recreational Resources program.
The Sexual Health Program provides education, consultation and personalized rehabilitation for patients and their partners who have experienced changes in sexual health during and after cancer treatment.
Through all stages of cancer treatment and survivorship, our Spiritual Care staff is available 24 hours a day to provide emotional and spiritual support for adults and pediatric patients and family members.
Young adults with cancer face very different challenges than patients who were diagnosed earlier in childhood or later in adulthood. The Young Adult Program can help you to find the resources and expertise available at Dana-Farber to help support your cancer experience.
Integrative therapies, also known as complementary therapies, range from acupuncture and massage to nutritional guidance and music therapy. Patients treated at the Zakim Center credit its services with easing nausea, improving circulation, and reducing pain, stress, and anxiety associated with cancer treatment.
In this video, Dr. Daniel DeAngelo talks about his work with stem cell transplant patients in the Hematologic Oncology Treatment Center at Dana-Farber/Brigham and Women's Cancer Center.