Longitudinal Study of Immune Mediated Disorders After Allogenic Hematopoietic Cell Transplantation (HCT)

Allogeneic hematopoietic cell transplantation (HCT) is the only known curative option for many hematologic disorders. After transplantation, many patients develop immune mediated disorders that may be life-threatening. Post-HCT immune mediated disorders are rare relative to other diseases but the prototype of graft versus host disease (GVHD) develops in 30-70% of patients. The morbidity and mortality associated with these HCT-associated immune mediated disorders are major barriers to successful use of transplantation to cure rare hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic/myeloproliferative syndromes amongst other diseases.

The purpose of this study is to characterize and more completely define the onset and course of immune mediated disorders after allogeneic HCT, focusing on participants who develop cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS), late acute graft-vs.-host disease (GVHD), and chronic GVHD.

• Of the participants undergoing allogeneic hematopoietic cell transplantation (HCT), can we, the researchers better identify who will develop immune-mediated disorders, what types of disorders participants will have, and whether these disorders will be severe or respond to currently available therapies?

This is a longitudinal study of 1118 individuals (1081 adults and 100 children). Those participating in this study will be evaluated over a 3 year period at 9 study sites. Participants will be enrolled pre-transplant, or up to day 121 post transplantation. This wide enrollment window will allow sites to use recruitment methods that are most efficient at their institutions. At least 2 years of follow-up will ensure an adequate sample size, and sufficient time for observation of the full spectrum of immune mediated disorders.

• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
• Total number of consented subjects: 159
• Subject Sample Telemetry Report (SSTR)

• Clinical Trials
  • NCT01206309

Inclusion criteria:

1. Planned or completed first allogeneic stem cell transplant (any conditioning regimen, graft source, donor type and GVHD prophylaxis regimen)
2. Signed, informed consent and, if applicable, child assent

Exclusion Criteria:

1. Inability to comply with study procedures
2. Anticipated survival less than 6 months due to co-morbid disease
3. Autoimmune disorder before HCT and active within the past 5 years, or inherited immunodeficiency
4. Diagnosis of late acute or chronic GVHD prior to study enrollment
5. Hematologic relapse or chemotherapy refractory disease at restaging within 1 month of HCT or at the time of enrollment (e.g., > 5% blasts for leukemia; poorly responsive lymphoma)

• Study Activated February 25, 2011
• First Accrual March 14, 2011
• Last DSMB review May 01, 2014
• Next DSMB review - N/A (consortium closed)

• Primary Phenotype: Graft vs Host Disease
• Bronchiolitis Obliterans

• Study Chairs
  • Stephanie Lee, MD, PhD. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Mukta Arora, MD. University of Minnesota, Minneapolis, MN, USA.
• Participating Site Principal Investigators
  • Corey Cutler, MD, MPH. Dana-Farber Cancer Institute, Boston, MA, USA.
  • Sally Arai, MD, MS. Stanford University, Stanford, CA, USA.
  • Joseph Pidala, MD. H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Madan Jagasia, MD. Vanderbilt University, Nashville, TN, USA.
  • Jeanne Palmer, MD. Medical College of Wisconsin, Milwaukee, WI, USA.
  • Iskra Pusic, MD. Washington University St. Louis, St. Louis, MO, USA.
• Current Funding Source
  • U54-CA163438. National Institutes of Health, Bethesda, MD, USA.