Read this patient's reflections on her experience.
In 2003, a then-48-year-old woman who is an avid distance runner presented to her primary care physician after noticing unusual fatigue during a 10-kilometer race. A complete blood count was notable for a white cell count of 14 x 109/L, hematocrit of 28%, and a platelet count of 115 x 109/L. She was referred to a hematologist for further evaluation. A bone marrow biopsy was consistent with poorly differentiated acute myeloid leukemia (AML) with normal cytogenetics and absence of NPM1 and FLT3 mutations.
The patient was then referred to Dana-Farber/Brigham and Women's Cancer Center under the care of Daniel DeAngelo, MD, PhD, of the Adult Leukemia Program. The patient opted to participate in the randomized trial CALGB 19808, which was testing whether the P glycoprotein multidrug resistance (MDR) inhibitor PSC-833 (valdospar) improved outcomes for patients with AML under age 60.
After receiving induction chemotherapy with daunorubicin, etoposide, cytarabine, and PSC-833, and being successfully treated for an Aspergillus pneumonia, she entered a complete remission and went on to an autologous transplant on protocol. Since the patient lacked an HLA-identical sibling and had a normal karyotype without a FLT3 mutation, allogeneic transplant was not pursued.
She did very well initially after autologous transplant. In July 2007, however — nearly four years after her initial diagnosis — the patient was noted to have neutropenia. A repeat bone marrow biopsy at that time confirmed relapse of AML. She underwent reinduction chemotherapy with daunorubicin and cytarabine and entered a second complete remission. An unrelated, HLA-matched donor was identified. The patient went on to receive a reduced-intensity transplant (conditioning with fludarabine and busulfan) with peripheral blood stem cells in October 2007 under the care of transplant physician Edwin Alyea, MD.
Unfortunately, in April 2008, the patient developed pancytopenia. A repeat bone marrow biopsy was markedly hypocellular and without evidence of relapse. Chimerism had been 98% donor at the end of March 2008, but declined to 40% by the end of April 2008, consistent with late graft failure. She was readmitted for a second reduced-intensity transplant, using the same donor as the first allogeneic transplant, in June 2008. This time, she received conditioning with fludarabine, busulfan and anti-thymocyte globulin, and tolerated it well. Her blood counts successfully recovered.
Six months after her second allogeneic transplant, the patient's peripheral blood counts again declined. A repeat bone marrow biopsy demonstrated second relapse of AML. She was readmitted to Brigham and Women's Hospital with fever and neutropenia in December 2008, and did not re-emerge for four months. She underwent another induction chemotherapy with a high-dose cytarabine-based regimen and had multiple life-threatening infections, including pulmonary aspergillosis and cytomegalovirus (CMV) colitis with a related gastrointestinal bleed.
Other complications included delirium and severe edema. Once recovered from these complications, the patient underwent a third reduced-intensity allogeneic transplant using a different unrelated donor. She received conditioning with fludarabine and melphalan. She recovered slowly from this and was finally able to go home in April 2009.
The patient has since developed graft-versus-host disease (GVHD) of the upper gastrointestinal system and liver, which has responded to pulses of prednisone. Over the past four years, she has remained in remission from her AML, although she underwent a partial nephrectomy for a renal cell carcinoma and has had multiple squamous cell carcinomas of the skin removed.
Despite her long and complicated medical course, the patient is now doing very well in long-term follow-up — 11 years since her initial diagnosis of AML. She is physically active and continues to run and play tennis. She is also back to writing, traveling, and enjoying her family.
— Edwin Alyea, MD, and Melissa Cochran, MS, NP, of the Adult Stem Cell Transplantation Program