Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Treatment-Related Myelodysplastic Syndrome or Acute Myelogenous Leukemia

Abstract

The development of treatment-related myelodysplastic syndrome (tMDS) or treatment-related acute myelogenous leukemia (tAML) is a complication that can occur after chemotherapy or radiation therapy. Eighteen patients with a previous malignancy treated at our institution and three patients with a nonmalignant primary tumor received an allogeneic hematopoietic stem cell transplant (HSCT) on the pediatric bone marrow (BM) transplantation service for the treatment of tMDS/tAML over a 15-year period. Five patients proceeded to HSCT without induction chemotherapy. Fourteen patients received high-dose cytarabine according to the Capizzi II regimen as first-line induction therapy with 13 of them achieving complete remission (CR) or refractory anemia (RA) with persistent cytogenetic abnormalities after this treatment. Two patients received an anthracycline-based induction therapy. Conditioning regimens were selected according to previous therapies: 11 patients received busulfan-melphalan-fludarabine (BU-MEL-FLU), which consisted of busulfan (0.8 mg/kg/dose every 6 hours ×10 doses), melphalan (70 mg/m(2)/dose × two doses), and fludarabine (25 mg/m(2)/dose × five doses) for cytoreduction; three patients received a total body irradiation (TBI)-containing regimen; seven patients received myeloablative regimens containing busulfan and/or melphalan and/or thiotepa with doses modified for organ toxicity. Sixteen patients received T cell-depleted (TCD) grafts; four patients received unmodified grafts; one patient received a double-unit cord blood transplantation (DUCBT). Donors included HLA-matched (n = 9), or mismatched (n = 3) related donors, or HLA-matched (n = 4), or mismatched (n = 4) unrelated donors, or DUCBT (n = 1). Disease status at the time of HSCT was: morphologic and cytogenetic CR (n = 12); RA with positive cytogenetics (n = 6); and refractory disease (n = 3). With a median follow-up of 5.9 years (2.2-15.7 years), the 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire group were 61.1% with 12 patients alive without evidence of either primary disease or tMDS/tAML. The OS and DFS rate for the 11 patients who received the BU-MEL-FLU cytoreduction with TCD grafts was 54.5%. DFS was 65.7% for patients in RA or CR at HSCT compared with 0% for patients with >5% residual marrow blasts (P = .015). Nine patients died; the cause of death was relapse of MDS/AML (n = 4) or primary disease (n = 2), graft-versus-host disease (GVHD; n = 2), and infection (n = 1). Four patients developed grade II to IV acute GVHD. One patient developed localized chronic GVHD. Our results suggest that the strategy of induction with high-dose cytarabine therapy followed by allogeneic stem cell transplantation improves the overall outcome for patients with tMDS/tAML. In addition, the use of a TCD transplantation with BU-MEL-FLU as cytoreduction may decrease the toxicity of transplantation in heavily pretreated patients without an increase in relapse rate.

Allogeneic hematopoietic stem cell transplantation for nonmalignant hematologic disorders using chemotherapy-only cytoreductive regimens and T-cell-depleted grafts from human leukocyte antigen–matched or –mismatched donors

“…The first aim was to avoid the use of radiation in patients and especially children with non-malignant disorders as there was no need for its anti-leukemic effect, while using chemotherapeutic and immunosuppressive agents achieve the necessary myelosuppression and immunosuppression. We used two common chemotherapy regimens as stated above and previously described in other transplant series for malignant disorders [20, 21]. …”

Dyskwalifikacja dawcy komórek krwiotwórczych w trakcie chemioterapii wysokodawkowanej u biorcy przygotowywanego do transplantacji: propozycja algorytmu postępowania ratunkowego

“…W związku z wcześniejszymi powikłaniami po konwencjonalnej chemioterapii u pacjentki zaplanowano chemioterapię ze zredukowaną intensywnością, wg protokołu zawierającego busulfan dożylny 3,2 mg/kg/dobę (w dniach -12, -11, -10), melfalan 70 mg/kg/dobę (w dniach -10, -9), fludarabinę 25 mg/ m 2 /dobę (w dniach -9, -8, -7, -6, -5) oraz globulinę antytymocytarną (Thymoglobulin, Genzyme) 8 mg/kg/3 doby (w dniach -3, -2, -1) [2].…”

Levetiracetam as a possible cause of secondary graft failure after allogenic hematopoietic stem cell transplantation

“…Hematopoietic stem cell transplantation is a curative treatment option for children with treatment-related myelodysplastic syndrome. 3,4 Secondary graft failure, the loss of donor cells after initial engraftment, is a relatively uncommon but serious and life-threatening complication after pediatric hematopoietic stem cell transplantation, occurring in 2.2% of patients. 5 Here we report a case of secondary graft failure after hematopoietic stem cell transplantation for treatment-related myelodysplastic syndrome during antiepileptic treatment with levetiracetam.…”