Reduced Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (PIDs) (BMT Clinical Trials Network 1204)

Status: Recruiting
Diagnosis: Pediatric Hematopoietic Stem Cell Transplant (HSCT)
NCT ID: NCT01998633 (View complete trial on
DFCI Protocol ID: 13-586


HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent primary immune disorders that are typically fatal without Hematopoietic Cell Transplant (HCT). However, transplant is often complicated by inflammation, infection and other co-morbidities. In addition, these disorders have been shown to be cured with partial chimerism, making them an ideal target for the use of reduced intensity approaches, where a portion of patients may not achieve full donor chimerism, but instead achieve stable mixed chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH (Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and unstable chimerism remain challenges. An institutional case series from Cincinnati Children's Hospital demonstrated full or high-level chimerism and improved durable engraftment using intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH as well as other primary immunodeficiencies where allogeneic transplant with RIC has been shown to be feasible and stable chimerism is curative.


Conducting Institutions:
Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:
Christine Duncan, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,

Eligibility Criteria

Inclusion Criteria: 1. Patient is ≥ 4 months and ≤ 45 years of age at time of enrollment. 2. Meets criteria for one of the following immune disorders (2A-2F) requiring HCT: 2A. HLH or related disorder with indication for HCT. 2B. CAEBV: Patients with chronic EBV infection (CAEBV) with or without associated lymphoma (in complete remission) or active HLH. Note that this diagnosis is distinct from post-transplant lymphoproliferative disorder/ EBV-associated lymphoproliferative disease (PTLD/LPD). 2C. Chronic granulomatous disease with indication for HCT. 2D. X-linked Hyper IgM Syndrome (HIGM1). 2E. IPEX Syndrome. 2F. Severe Leukocyte Adhesion Deficiency, type I (LAD-I). 3. Lansky or Karnofsky performance status ≥ 50%. 4. Human Leukocyte Antigen (HLA) typing of related donors must be a 6/6 match for HLA-A and -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) OR a 7/8 or 8/8 match for HLA-A, -B, -C, and -DRB1 (at high resolution using DNA-based typing). Unrelated donors must be a 7/8 or 8/8 match at HLA-A, -B, -C, and -DRB1 (at high resolution using DNA-based typing). Only bone marrow stem cells are allowed. 5 Patient must have adequate organ function as measured by: 1. Cardiac: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction (LVSF) > 26% by echocardiogram. 2. Renal: Calculated or radioisotope Glomerular filtration rate (GFR) > 50 mL/min/1.73m2 3. Hepatic: Adequate liver function: serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory (with the exceptions of isolated hyperbilirubinemia due to Gilbert's syndrome, or hyperbilirubinemia as the result of liver inflammation in the setting of persistent, active HLH); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 10x upper limit of normal as per local laboratory (with the exception of elevated transaminase levels as the result of liver inflammation in the setting of persistent, active HLH). 4. Pulmonary: Patient may not be on mechanical ventilation support or have progressive pulmonary infection at the time of transplant; Pulmonary Function Testing (PFT) with Forced Expiratory Volume (in 1 second) (FEV1) > 50% of normal and Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) corrected for Hgb > 50% of normal. Patients unable to undergo PFTs should have stable respiratory status with Saturated Oxygen (SaO2) > 90% on a maximum of 2L/min supplemental oxygen. 6. Signed informed consent. Exclusion Criteria: 1. Hematopoietic stem cell transplant within 6 months of enrollment. 2. Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement) at time of enrollment. We recognize that patients with CAEBV may have ongoing EBV viremia at the time of initiating transplant therapy, but other patients should have no uncontrolled bacterial, viral or fungal infections at the time of enrollment. 3. Pregnant or breastfeeding. 4. Seropositive for human immunodeficiency virus (HIV). 5. Alemtuzumab within 2 weeks of enrollment.
  • Email
  • Print
  • Share
  • Text
Highlight Glossary Terms
  • Make an Appointment

    • For adults:
      877-442-3324 (877-442-DFCI)

    • Quick access:
      Appointments as soon as the next day for new adult patients

    • For children:
      888-733-4662 (888-PEDI-ONC)

    • Request Appointment Online