High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia

Abstract

We evaluated 190 children with very highrisk leukemia, who underwent allogeneic hematopoietic cell transplantation in 2 sequential treatment eras, to determine whether those treated with contemporary protocols had a high risk of relapse or toxic death, and whether non-HLA-identical transplantations yielded poor outcomes. For the recent cohorts, the 5-year overall survival rates were 65% for the 37 patients with acute lymphoblastic leukemia and 74% for the 46 with acute myeloid leukemia; these rates compared favorably with those of earlier cohorts (28%, n ‫؍‬ 57; and 34%, n ‫؍‬ 50, respectively). Improvement in the recent cohorts was observed regardless of donor type (sibling, 70% vs 24%; unrelated, 61% vs 37%; and haploidentical, 88% vs 19%), attributable to less infection (hazard ratio [HR] ‫؍‬ 0.12; P ‫؍‬ .005), regimen-related toxicity (HR ‫؍‬ 0.25; P ‫؍‬ .002), and leukemiarelated death (HR ‫؍‬ 0.40; P ‫؍‬ .01). Survival probability was dependent on leukemia status (first remission vs more advanced disease; HR ‫؍‬ 0.63; P ‫؍‬ .03) or minimal residual disease (positive vs negative; HR ‫؍‬ 2.10; P ‫؍‬ .01) at the time of transplantation. We concluded that transplantation has improved over time and should be considered for all children with very high-risk leukemia, regardless of matched donor availability. (Blood. 2011;118(2):223-230)

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

“…24,26,28 Our data suggest that both approaches provide similar transplant outcomes, a conclusion also reached by other groups. 19 Leung et al 20 also demonstrated that, for children with acute leukemia, modern haploidentical HCT provides similar outcomes to both matched sibling and unrelated donor HCTs. Their results, in combination with ours and others, 19,21 suggest that haploidentical HCT should be more widely utilized for patients with otherwise incurable diseases.…”

“…4,17,18 However, combining CD34-selected haploidentical cells with a fully myeloablative conditioning regimen for patients with malignancy has been more fully explored in adult patients, 1,2 though some pediatric reports exist. [19][20][21] Fewer reports have focused on children with life-threatening nonmalignant diseases, [21][22][23] where the use of UCB stem cells predominates because many children are an appropriate size to receive the small cell dose in an UCB unit. For larger children and adults, two UCB units can be combined.…”

Long-term outcomes of unmanipulated haploidentical HSCT for paediatric patients with acute leukaemia

“…6,7 The latest reports of T-cell depletion HSCT from HID parental donors showed improved outcomes in the recent treatment era, with 5-year OS rates of 65% and 74% for very high-risk ALL and AML patients, respectively. 8 At our institution, promising results with unmanipulated, HID HSCT have been achieved in adult patients without ex vivo T-cell depletion, demonstrating outcomes similar to those with MSDs and well-matched unrelated HSCT. 9,10 The short-term efficacy and safety of this HID transplantation setting was also reported in 42 paediatric patients, including 36 patients with acute leukaemia.…”

“…Twenty-five patients died of relapse. Among eight patients who received chemotherapy or radiation therapy followed by modified DLI, seven (four with haematological relapse and three with extramedullary relapse) were alive at a median follow-up of 15 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) months after the diagnosis of relapse. Among the 12 AML patients who had haematological relapses, 2 received chemotherapy, followed by modified DLI, but they died of relapse at 4 and 6 months after their relapses, respectively.…”

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

“…[1][2][3] Allogeneic hematopoietic stem cell transplantation from either related or unrelated donor remains indicated either for patients in first complete remission (CR) but at very high risk of relapse or for patients who experience leukemia recurrence. 4 Unrelated cord blood transplantation (UCBT) has been explored as an alternative option for patients without a suitable human leukocyte antigen (HLA)-matched donor. 5 Tolerance of some degree of HLA mismatch, with relatively low rates of both acute and chronic graft versus host disease (GvHD), makes UCBT an attractive option for children.…”