Allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of children with very high risk (VHR) acute lymphoblastic leukemia (ALL) in first remission (CR1) Meeting Abstract

Authors: Boulad, F.; Kernan, N. A.; Steinherz, P. G.; Prockop, S. E.; Scaradavou, A.; Small, T. N.; Kobos, R.; Shukla, N.; Doorish, C.; O'Reilly, R. J.
Abstract Title: Allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of children with very high risk (VHR) acute lymphoblastic leukemia (ALL) in first remission (CR1)
Meeting Title: 52nd Annual Meeting of the American Society of Hematology (ASH)
Abstract: Between August 1988 and December 2009, 40 pediatric patients (pts) received an allogeneic HSCT for the treatment of very high risk ALL in CR1. They were 22 males and 18 females, aged 0.8 -19.2 years (median 10.0). Thirty eight patients had very high risk features: high white cell count greater than 200,000/mm3 (N=7), hypodiploidy (N=6), including double hypodiploidy (N=3), high risk cytogenetics with t(9;22) (N=14) or Mixed Lineage Leukemia (MLL) (N=3), and induction failure (N=23). Induction failure was defined morphologically by a single marrow aspirate revealing greater than 35% blasts by day +7 of induction, or greater than 5% blasts by day +14 or day +28 of induction. The remaining two patients included one infant ALL with a WBC >100,000/mm3 and one patient with ALL, Evans Syndrome and a prior CNS hemorrhage and fungal infection. Twenty two patients had one VHR feature while 16 patients had two VHR features: Patients received marrow or peripheral blood stem cell transplants from HLA-matched siblings (N=14) or volunteer unrelated donors (N=21) or unrelated double cord blood transplants (N=5). Unrelated donors were HLA-matched for 12 pts, but mismatched for nine pts at one (N=6) or two Class I antigens (N=3). All cord blood donors were matched at 4 or 5/6 HLA-antigens. Twenty three Patients received T-cell depleted grafts. following cytoreduction with hyperfractionated total body irradiation (HF-TBI) 1,375-1,500 cGy, Thiotepa (Thio) 5 mg/Kg/day X 2 and Cyclophosphamide (CY) 60 mg/Kg/day X 2. Grafts were marrow T-cell : depleted with soy bean agglutinin and e-rosetting for 15 patients or peripheral blood stem cells T-cell depleted by CD34 selection and E-rosetting for 8,patients. Twelve pts received unmodified grafts following cytoreduction with a TBI-CY based regimen (N=8) or chemotherapy regimen (N=4). Five patients received double cord blood grafts following HF-TBI 1,375 cGY, Fludarabine 25 mg/m(2)/day X 3 and CY 60 mg/Kg/day X 2. Graft-versus-host-disease (GvHD) prophylaxis for the BMT recipients included cyclosporine (CSA) + methotrexate or steroids, and for the cord blood recipients, CSA and mycophenolate mofetil.With a median follow-up of 11.1 years (range 0.6-21.9 yrs), the 10-year overall survival and disease-free survival of the entire cohort were 78% and 70% respectively, and 80% and 72% respectively when excluding the accidental death. Two recipients of T-cell depleted grafts suffered a graft failure (one early and one late), both of whom received a secondary T-cell depicted graft from a (different) mismatched related donor, engrafted and are alive and well. Two recipients of unmodified marrow grafts relapsed 4.9, and 18.9 months post BMT, one of whom is still alive disease free following treatment with chemotherapy. One recipient of:a double cord blood graft relapsed three months post transplant. The overall risk of relapse for the entire cohort was 15%. Six pts died; cause of death was: relapse (N=2), secondary malignancy (N=2), acute GvHD (N=1), and accidental death: (head trauma) (N=1). Grade 2-4 GvHD was diagnosed in recipients of unmodified grafts (N=3), double cord blood graft (N=2) and T-cell depleted grafts (N=1). The OS and DFS for recipients of T-cell depleted transplants following TBI THIO CY were both 83% with a 0% relapse rate.In summary, the outcome of allogeneic HSCT for children with very high risk ALL in CR1 in our series appears to be superior to that reported with chemotherapy for patients with these very high risk features. Moreover, the use of hyperfractionated TBI, Thio and CY followed by T-cell depleted grafts from related or unrelated donors was associated with a very good outcome with no relapse and minimal GvHD.
Keywords: disease relapse; disease remission
Journal Title: Blood
Volume: 116
Issue: 21
Meeting Dates: 2010 Dec 4-7
Meeting Location: Orlando, FL
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-11-19
Start Page: 1458
End Page: 1459
Language: English
PROVIDER: biosis
PUBMED: 22276300
Notes: --- - Meeting Abstract: 3546 - 52nd Annual Meeting of the American-Society-of-Hematology (ASH) - Orlando, FL, USA - December 04 -07, 2010 - Amer Soc Hematol - "Source: Biosis"