Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Abstract

Summary:The objective of this study is to investigate the outcome of children 24 months of age or younger (infants) at the time of allogeneic bone marrow transplantation (BMT) for acute leukemia or myelodysplasia. We analyzed the survival rate, prognostic factors, incidences of late sequelae, and immune reconstitution in 22 infants who underwent allogeneic BMT. The 5-year event-free survival estimate was 45.5% (95% confidence interval (CI), 24.4% to 63.3%). Six patients died of transplant-related complications and six died of disease relapse. Remission status at the time of BMT was the most important prognostic factor (P ‫؍‬ 0.005): no patient who received a transplant while their disease was not in remission survived, whereas the 5-year survival estimate for infants who underwent BMT during remission was 56% (95% CI, 31% to 75%). Long-term outcomes in the 10 infant survivors were compared with those of 10 older controls matched for diagnosis, disease status at the time of BMT, calendar year at the time of BMT, and source of stem cells. Immune function 1 year after transplantation and the incidences and spectra of late sequelae were similar for both groups during a median of 3.5 years (range, 1.5 to 7.2 years) of follow-up. Bone Marrow Transplantation (2001) 27, 717-722. Keywords: allogeneic transplantation; infant leukemia; myelodysplastic syndrome; late sequelaeThe incidences of lymphoid and myeloid leukemias in infants are approximately equal. Acute lymphoblastic leukemia (ALL) in infants accounts for 2.5% to 5% of all cases of childhood ALL, and acute myeloid leukemia (AML) in infants accounts for 6% to 14% of all cases of childhood AML. 1 The frequent presence of poor prognostic factors such as 11q23/MLL rearrangement in ALL and a high leukocyte count at the time of diagnosis of AML results in an overall long-term survival of only approxiCorrespondence: WH Leung,

Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia

“…22 Our study confirms that reported by others who have demonstrated that phase of disease is the most important factor determining outcome after HC transplantation. 19,22 In our series, the major cause of failure was relapse of disease. Sixteen of 40 patients relapsed after transplantation with the highest relapse incidence occurring in patients with advanced disease at time of transplantation.…”

Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group

“…[19][20][21][22][23][24][25][26][27] Pui et al 19 retrospectively analyzed cooperative group and individual transplant center data for children with ALL and 11q23 abnormalities, concluding that any type of HSCT was associated with a worse outcome than chemotherapy alone for t(4;11)-positive leukemia. In that study, the EFS rate for the 28 infants who underwent HSCT was only 1973%, which is extremely low compared to our results and those of Sanders et al, 27 who reported a 3-year disease-free survival rate of 42.2% among 40 infants with ALL following HSCT.…”

“…A total of 102 patients were registered on two consecutive multicenter trials, designated MLL96 and MLL98, between 1995 and2001. Those with a rearranged MLL gene (MLL-R, n ¼ 80) were assigned to receive intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with germline MLL (MLL-G, n ¼ 22) were treated with chemotherapy alone.…”

Determinants of Antileukemia Effects of Allogeneic NK Cells

“…Three MLL-rearranged lines were chosen, because one expressed HLA-C Asn80 alone (MLL-1), another expressed HLA-C Asn80 and HLA-C Lys80 (MLL-2), and the third expressed HLA-C Asn80 , HLA-C Lys80 , and HLA-B Bw4 (MLL-3): MLL-1 (B8, B62, Cw03, Cw07), MLL-2 (B14, B18, Cw08, Cw15), and MLL-3 (B14, B37, Cw06, Cw08). We are interested in studying leukemias with MLL rearrangement because they are common in infant and secondary leukemias that are highly resistant to conventional chemotherapy (25,26) and may benefit from novel therapeutic strategies (27). We investigated the determinants of NK cell cytotoxicity toward these leukemia cells to develop a new treatment approach.…”