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LAST MONTH’S CLINICAL CHALLENGE

 

A 40-year old otherwise healthy man was diagnosed with chronic myeloid leukemia in first chronic phase six months ago after a routine annual examination.  He took imatinib mesylate for three months but experienced intolerable side effects that resolved with discontinuation of the drug.  He is about to undergo a myeloablative transplant from his HLA-matched brother.  Which stem cell source would you recommend?


YOUR RESPONSES

 
  • Bone marrow – 58% 

  • Perhipheral blood – 42%

     
       


Commentary Provided by Mary Eapen, MBBS
Medical College of Wisconsin

 

Among adults, peripheral blood grafts are the main stem cell source for both related and unrelated donor transplants.  Some reports including randomized clinical trials suggest transplantation of peripheral blood progenitor cells (PBPC) from an HLA-matched sibling may offer advantages over the transplantation of bone marrow (BM) in terms of leukemia-free and overall survival.1,2,3  All of these reports documented faster rates of hematopoietic recovery after transplantation of PBPC compared to BM.  However, chronic graft-versus-host disease (GVHD) rates are higher after transplantation of PBPC than after BM.1,4,5  In patients with chronic myeloid leukemia in first chronic phase the early leukemia-free and overall survival rates are similar after PBPC and BM transplants.1,2 

 

However, observational studies suggest when these patients are followed for a longer period (>6 years), the rates of transplant-related mortality, treatment failure (inverse of leukemia-free survival) and overall mortality are higher after PBPC compared to BM transplants.5 Shown below are six-year leukemia-free survival rates (61% vs. 41%) after BM and PBPC transplants, respectively for patients reported to the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation.5  Patients included in this report5 were initially reported in 20001 (early transplant outcomes, median follow up one year).

 

In a small study, granulocyte mobilized BM was associated with hematopoietic recovery rates comparable to PBPC grafts and lower rates of chronic GVHD but without a survival advantage.6   However, the optimal dosing and scheduling of growth factor before harvest and long-term outcome after transplantation of mobilized BM is yet to be determined.  

 

Otherwise healthy patients with chronic myeloid leukemia in first chronic phase have relatively low transplant-related mortality and relapse rates after transplantation of BM, leaving little to gain from faster recovery of hematopoiesis and higher chronic GVHD with PBPC.  Therefore, I would favor transplantation of a BM graft for this patient.

 

 

 

References

 

  1. Champlin RE, Schmitz N, Horowitz MM, et al.  Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation.  Blood, 2000, 95: 3701-3709
  2. Bensinger WI, Martin PJ, Storer B, et al.  Transplantation of bone marrow as compared with peripheral blood cells from HLA-identical relatives in patients with hematologic cancers.  N Engl J Med, 2001, 344: 175-181
  3. Stem Cell Trialists Collaborative Group.  Allogeneic peripheral blood stem cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials.  J Clin Oncol, 2005, 23: 5074-5087
  4. Flowers MED, Parker PM, Johnston LJ, et al.  Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow up of a randomized trial. Blood, 2002, 100: 415-419
  5. Schmitz N, Eapen M, Horowitz MM, et al.  Long-term outcome of patients given transplants of mobilized blood or bone marrow: A report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation.  Blood, 2006, 108: 4288-4290
  6. Morton J, Hutchins C and Durrant S.  Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells.  Blood, 2001, 98: 3186-3191