Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research

Abstract

In children with acute lymphoblastic leukemia (ALL) with isolated central nervous system (CNS) relapse and a human leucocyte antigen (HLA)-matched sibling, the optimal treatment after attaining second remission is unknown. We compared outcomes in 149 patients enrolled on chemotherapy trials and 60 HLA-matched sibling transplants, treated in 1990-2000. All patients achieved a second complete remission. Groups were similar, except the chemotherapy recipients were younger at diagnosis, less likely to have T-cell ALL and had longer duration (X18 months) first remission. To adjust for time-totransplant bias, left-truncated Cox's regression models were constructed. Relapse rates were similar after chemotherapy and transplantation. In both treatment groups, relapse rates were higher in older children (11-17 years; RR 2.81, P ¼ 0.002) and shorter first remission (o18 months; RR 3.89, Po0.001). Treatment-related mortality rates were higher after transplantation (RR 4.28, P ¼ 0.001). The 8-year probabilities of leukemiafree survival adjusted for age and duration of first remission were similar after chemotherapy with irradiation and transplantation (66 and 58%, respectively). In the absence of an advantage for one treatment option over another, the data support use of either intensive chemotherapy with irradiation or HLA-matched sibling transplantation with total body irradiation containing conditioning regimen for children with ALL in second remission after an isolated CNS relapse.

Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus

“…Mice were fed Diet Gel recovery (Clear H 2 O) and kept on antibiotics [560 μg/L polymixin B (Bupha), 700 μg/L ciprofloxacin (Bayer), 800 μg/L amphotheracin B (Bristol-Myers Squibb)] in autoclaved acidified drinking water until white blood cell counts were recovered at 4 wk posttransplant. Blood samples were obtained at 4,8,12,16, and 21 wk by lateral tail vein incision. At 16 or 21 wk, mice were killed by O 2 /CO 2 inhalation and thymus, BM, PB, and spleen were isolated.…”

“…These marked HSCs were transplanted, using an optimized protocol (10), into NOD/SCID/Il-2Rγ −/− (NSG) mice (11), which allowed us to determine the dynamics of clonal reconstitution in the thymus in great detail. We used umbilical cord blood (UCB) as source of human stem cells, because UCB is frequently used as a readily available HSC source with less stringent HLA (human leukocyte antigen)-matching requirements (12). However, T-cell immune reconstitution, a general problem in allogeneic HSCT, is more problematic in UCB.…”

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…[1][2][3][4][5][6][7][8][9] However, the treatment is still controversial for low-risk relapses, which either involve extramedullary sites only and/or occur late in the BM. [10][11][12][13][14] Autologous transplantation may be an alternative to chemotherapy for ALL in CR2 after low-risk relapse. [15][16][17][18][19][20][21][22][23][24][25] In 2001, we reported a study that showed the feasibility and efficacy of an innovative protocol for autologous transplantation of purified peripheral hematopoietic stem cells in 12 pediatric patients with pediatric B-cell-precursor ALL after isolated extramedullary and/or late relapse.…”

Recent Advances in Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia

“…A collaborative study by COG and the Center for International Blood and Marrow Transplant Research (CIBMTR) showed that the 8-year leukemia-free survival, adjusted for age and duration of first remission, was similar after chemotherapy with neuraxis irradiation (66%) and HSCT (58%) [18]. A Minnesota team, on the other hand, reported an absence of leukemia relapse, with 91% leukemia-free survival, in patients undergoing transplantation for isolated CNS relapse [19].…”