Ninety-seven children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) received HLA-identical bone marrow transplants from sibling donors, after preparation with 1320 cGy of hyperfractionated total-body irradiation and high-dose cyclophosphamide. Kaplan-Meier product-limit estimates (means +/- SE) of disease-free survival at five years among patients with ALL in second remission, third remission, and fourth remission or relapse were 64 +/- 9, 42 +/- 14, and 23 +/- 11 percent, respectively, with probabilities of relapse of 13 +/- 7, 25 +/- 13, and 64 +/- 16 percent. Among patients with AML in first remission, second remission, and third remission or relapse, five-year disease-free survival estimates were 66 +/- 10, 75 +/- 15, and 33 +/- 19 percent, with respective relapse probabilities of 0, 13 +/- 12, and 67 +/- 19 percent. The most frequent cause of death in patients in early remission (ALL in second or third remission or AML in first or second remission) was bacterial sepsis, fungal sepsis, or both, most often in the presence of acute or chronic graft-versus-host disease. Among patients with ALL who received transplants while in second remission, the duration of the initial remission had no effect on the probability of relapse after transplantation. The only pretransplantation factor that significantly affected outcome was the disease status at the time of transplantation; patients in early remission had better disease-free survival. We conclude that transplantation after preparation with hyperfractionated total-body irradiation and cyclophosphamide is an effective mode of therapy in children with refractory forms of acute leukemia.
Summary:engraftment after high-dose chemotherapy compared to autologous BM. Allogeneic transplants with PBSC have also been shown to provide hastened tri-lineage Growth factor administration to donors prior to bone marrow (BM) harvesting results in an enrichment of the engraftment. 1,2 However, there is a growing concern that unmanipulated allogeneic PBSC transplants may lead to a graft for myeloid precursors. In animals, growth factorprimed BM has a higher repopulating ability than higher incidence of graft-versus-host disease (GVHD) especially of chronic extensive GVHD. 3 Intriguingly, the untreated BM. Ten patients received an HLA-identical sibling, allogeneic transplant using granulocyte colonyincidence of GVHD after allogeneic PBSC transplantation seems not to correlate with the number of T lymphocytes stimulating factor (G-CSF)-stimulated BM. Stimulation consisted of G-CSF at 10 g/kg/day for 2 days prior to infused. 3 Furthermore, positive CD34 + cell selection of PBSC with concurrent depletion of T lymphocytes does not harvest. Patients were transplanted for various benign and malignant hematological conditions. The GVHD seem sufficient to eliminate GVHD. Whether the G-CSF PBSC mobilization schedules currently in use result in simultaneous enrichengraftment of white cells and platelets. On average they attained an ANC of у1 ؋10 9 /l 9 days earlier and ment of the stem cell and progenitor content of the BM, or simply in a shift of these cells from the BM to the peria platelet count of у20 ؋ 10 9 /l 6 days earlier than historical controls receiving unstimulated HLA-identical pheral blood, has not been elucidated. A small number of studies has been conducted to detersibling BM. Hospitalization was shortened by a mean of 10 days and transfusion requirements were modest. mine the progenitor content and engraftment capability of growth factor-stimulated BM. In mice, G-CSF and stem None of the patients developed severe GVHD or disease relapse. Two patients died of severe VOD post-BMT cell factor produce 10-fold or greater increase in the BM repopulating ability in competitive assays. 10 In human studand thus were unevaluable for platelet engraftment. A third patient died of TTP on day 76 post-BMT. Seven ies, an increased number of committed myeloid progenitors 11 and CD34 + cells 12 were documented in BM harvests patients are alive and well 49-585 days post-BMT. Stimulated BM may provide a valuable alternative to from stimulated donors. Two studies using interleukin-3 and G-CSF 13 or GM-CSF 14 -stimulated BM failed to show allogeneic BM and PBSC transplants. Ideal stimulation regimens need to be investigated.faster engraftment compared to unstimulated BM but a third study using G-CSF showed hastened engraftment.
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