Work

252: Outcome of allogeneic hematopoietic stem cell transplantation for pediatric patients with chronic myeloid leukemia

Year: 2007

Type: article

Abstract: Although allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling offers curative therapy for the small numbers of children who develop chronic myeloid leukemia (CML), less than one third of patients have an appropriately matched sibling. Alternative donor transplantation has had a higher procedure-associated risk, particularly for graft-versus-host disease (GVHD). We have attempted to reduce these risks by incorporating alemtuzumab (Campath 1H) into the preparative regimens for alternative donor grafts. Between 1996 and 2006, 19 pediatric CML patients were transplanted using either matched sibling (MSD; n = 9) or alternative donor (AD; 5 matched unrelated; 2 mismatched unrelated; 3 mismatched related). All recipients of MSD grafts were in chronic phase at the time of transplant as were 6 of the AD recipients; three of the AD recipients were in accelerated phase and 1 in chronic phase presenting in lymphoid blast crisis at the time of transplant. All recipients received myeloablative conditioning consisting of cyclophosphamide 45mg/kg x 2, cytarabine arabinoside 3g/m2 x 6 and TBI 1200-1400 cGy. In addition, AD recipients received either ex vivo partial T-cell depletion or Campath to achieve in vivo T-cell depletion in an effort to reduce the risk of GVHD. Five AD patients died; 4 patients in chronic phase and 1 patient in accelerated phase prior to transplant. One patient died from recurrent disease and the other 4 from complications of therapy: 1 engraftment failure; 1 poor engraftment and fungal disease; 1 cryptosporidium parasitemia; and 1 pulmonary hemorrhage with viral infections. After transplantation, 30% in each group (MSD and AD) required additional Gleevec or donor leukocyte infusions for BCR/ABL positivity. The Kaplan-Meier estimate of disease-free survival at 2 years was 78% for the entire cohort: 100% for the MSD group and 56% for the AD group. Only 1 patient (AD recipient) developed grade 3-4 acute GVHD and only 1 patient (AD recipient) developed extensive, chronic GVHD. We conclude that stem cell transplantation provides effective leukemia control and potential cure even for patients with advanced disease who lack an MSD. Regimen-related mortality remains an impediment to improved outcome for pediatric CML patients receiving stem cells from unrelated or mismatched donors.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.257