Search

This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n=92) or TBI, fludarabine (n=56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n=75), myelodisplastic syndrome (n=24), myelofibrosis (n=16), high-grade lymphoma (n=15) and others (n=18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P<0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant.

Preparative regimens without total body irradiation (TBI) have been reported for alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September 1994 and 7 June 1999 48 patients with advanced hematologic malignancies were conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and antithymocyte globulin (ATG). Donors were HLA mismatched family members (1-2 antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n = 40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete chimerism in 31/37 patients (85%). Acute GVHD grades III-IV were seen in 10/46 patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent disease (17%) and 18 of transplant-related complications (37%): main causes of TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients (46%) survive with a median follow-up of 877 days (287-1840). The actuarial 3-year survival is 49% for FAM and 42% for UD transplants. Results obtained with this regimen in unrelated grafts for advanced CML (n = 15) were not significantly different when compared to 21 concurrent UD grafts for advanced CML prepared with CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of alternative donor hemopoietic stem cells. Results are similar when using unrelated matched donors or partially mismatched family donors, and not significantly different when compared to patients conditioned with CY-TBI.

Transplant-related mortality (TRM) remains a major problem in older patients undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have therefore explored a less intensive conditioning in 33 patients with a median age of 52 years (range 43–60) transplanted from human leucocyte antigen (HLA)-identical siblings. The underlying disease was chronic myeloid leukaemia (n = 15), acute myeloid leukaemia (n = 6), myelodysplasia (n = 7) or a chronic lymphoproliferative disorder (n = 5); 15 patients (45%) had advanced disease. The regimen consisted of thiotepa (THIO; 10 mg/kg) on day -5 and cyclophosphamide (CY; 50 mg/kg) on days -3 and -2 (total dose 100 mg/kg). The source was bone marrow (BM) (n = 17) or granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) (n = 16), which were infused without manipulation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and a short course of methotrexate. Mean time to achieve a neutrophil count of 0·5 × 109/l was 17 d (range 11–23) and full donor chimaerism was detected in 79% of patients by day 100. Acute GVHD grade III or IV occurred in 3% of patients. Chronic GVHD was seen in 45% of patients, with a significant difference for PB (69%) compared with BM transplants (23%) (P = 0·009). For BM grafts, the actuarial 2-year TRM was 6%, the relapse 56% and survival 87%; for PB grafts, these figures were, respectively, 27%, 33% and 68%. Twenty-five patients are alive at a median follow-up of 762 d (range 216–1615) and 20 patients (60%) remain free of disease. Thirteen patients (39%) received donor lymphocyte infusion (DLI) either for persisting or relapsing disease and six patients had complete remission. In conclusion: (i) patients up to the age of 60 years can be allografted with reduced intensity conditioning; (ii) the procedure was associated with a low transplant-related mortality, particularly for bone marrow grafts, because of a lower risk of chronic GVHD; and (iii) DLI were required after transplant in half the patients for persisting disease or relapse. [ABSTRACT FROM AUTHOR]