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Haploidentical Stem Cell Transplants in Children With Acute Lymphoblastic Leukemia in First or Second Remission

Year: 2011

Type: article

Abstract: Allogeneic hematopoietic stem cell transplant (SCT) offers curative therapy to children with high-risk or relapsed acute lymphoblastic leukemia (ALL). Here, we report encouraging results using haploidentical related donor CD34+ selected (T-cell depleted) peripheral blood stem cell transplants in children with ALL in first or second remission (CR1 or CR2). From May 2002 to September 2009, we transplanted 17 children (13 male, 4 female) in CR1 (n = 6) and CR2 (n = 11) using primarily a fully myeloablative conditioning regimen consisting of cyclophosphamide 45mg/kg x 2 doses, cytarabine arabinoside 3gm/m2 x 6 doses and total body irradiation (TBI) 1400cGy (n = 12). Five patients received either a reduced-intensity regimen or busulfan-based regimen for clinical purposes (such as to avoid TBI exposure). All patients received alemtuzumab (3, 5 or 10mg/dose depending on body weight) during conditioning for in vivo T-cell depletion to promote engraftment and provide additional GvHD protection. If the infused T-cell dose was less than 5x104 CD3 cells/kg, no additional GvHD prophylaxis was administered. The median age at transplant was 9.9 years (range, 2.9 to 21.6) and median follow-up 44 months post SCT (range, 13 to 102). Median CD34+ cell dose infused was 1.14x107/kg (range, 0.49-6.83x107/kg) and median CD3+ T-cell dose was 3.08x104/kg (range, 1.8x104-1.6x105/kg). The rate of donor engraftment was 82.4% – 3 patients failed to achieve initial donor engraftment but did so after receiving subsequent haploidentical SCT. Eleven of 17 (65%) patients received additional T-cell therapies post SCT (donor lymphocytes for mixed chimerism, cytotoxic T-lymphocyte therapy or planned T-cell addback strategies to re-establish T-cell immune reconstitution) and 2 received additional CD34+ cells for poor graft function. Two-year disease-free survival for these children is 60.5%. Of the 5 children who died, 2 died of relapse and 3 of treatment-related causes, primarily infection. One patient with p53 mutation developed secondary MDS 2 years post SCT and is alive with disease. In conclusion, while this data is preliminary, haploidentical transplants using in vivo T-cell depletion with alemtuzumab and ex vivo T-cell depletion with CD34+ selection offers promising clinical results in children with ALL in CR1 or CR2. With the addition of new clinical immunotherapy trials post SCT, we hope to achieve even higher survival with decreased relapse and deaths related to viral infection.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2010.12.468