Haploidentical stem cell transplantation for acute leukemia

Abstract

Since March 1993, 133 patients with high-risk acute leukemia (66 AML, 67 ALL) have received a megadose of T-cell depleted hematopoietic stem cells. The 1993-95 conditioning protocol included TBI, thiotepa, ATG and CY for 36 patients who received an inoculum made up of lectin-separated bone marrow and PBPCs. After 1995, to minimise the extra-hematological toxicity of the conditioning and eliminate GvHD, we substituted fludarabine for CY in the conditioning and PBPCs were depleted of T-cells by a positive selection of the CD34+ cells using CellPro (n=44 patients) or, since January 1999, CliniMacs (n = 53 patients). A later modification to the protocol in January 1999 was the suspension of post transplant G-CSF. WORK IN PROGRESS: We report here the results in the last 53 acute leukemia patients all of whom were transplanted under our modified protocol. Ages ranged from 9 to 62 years with a median of 38 years for the 33 patients with AML and 23 for the 20 with ALL. All were at high risk because 25 were actually in relapse at transplant, 16 were in second or later CR and even the 12 patients in CR1 were at high risk because of the unfavourable prognostic features. Overall 52/53 patients (98%) engrafted. The TBI-Fludarabine-based conditioning was well tolerated even in the 14 patients between 45 and 62 years of age. There was no veno-occlusive disease of the liver and the incidence of severe mucositis was low. Even though no post-transplant immunosuppressive therapy was given, acute GvHD grade > or = II occurred in only 4 cases and only one progressed to chronic GvHD. Overall, 16 patients (30%) have died of non-leukemic causes. Relapses occurred mainly in patients who were already in relapse at transplant (12/25). Only 3 of the 28 who were in any CR at transplant have so far relapsed. As our group has already shown, donor-vs-recipient NK cell alloreactivity exerts a specific graft-vs-AML effect in the absence of GvHD. In fact, leukemia relapse was largely controlled in AML recipients whose donor was NK alloreactive, with only 2 out of 16 relapsing. To date, 13 of 18 AML (72%) and 5 of 10 ALL (50%) who were in any CR at transplant, survive disease-free while 4 of the 15 patients (16%) in relapse at transplant survive. The probability of event-free survival for patients transplanted in CR is 60% in the 18 AML patients and 38% in the 10 ALL. The probability of EFS was significantly better in the 16 AML patients whose transplant included donor vs recipient NK cell alloreactivity than in those whose transplant did not (70% vs 7%). In conclusion, given our current results, the most suitable candidate for the full haplotype mismatched transplant should be in early stage disease and selection of an NK alloreactive donor is recommended.

Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies

“…1,3,12 Although T-cell depletion and high-dose infusions of CD34 þ cells reduced the incidence of severe GVHD and improved the rate of engraftment, frequency of relapse and infections remained high and the long-term survival was poor. 13,14 The reported studies involved small numbers of patients without long-term followup despite several encouraging reports. 14,15 In the present study, all 171 patients achieved complete donor engraftment.…”

“…13,14 The reported studies involved small numbers of patients without long-term followup despite several encouraging reports. 14,15 In the present study, all 171 patients achieved complete donor engraftment. Although the number of T cells in the grafts was more than 1 Â 10 8 cells per kilogram of recipient weight in all patients (Table 2), the incidence of GVHD and deaths from GVHD was lower than expected.…”

Haplotype mismatched transplantation using high doses of peripheral blood CD34+ cells together with stratified conditioning regimens for high-risk adult acute myeloid leukemia patients: a pilot study in a single Korean institution

“…8 Moreover, the method requires the reduction of T-cell numbers to o1 Â 10 4 /kg, in order to prevent GvHD. Recent studies by the abovementioned researchers on ISH 2002 10 and IBMTR 2003 11 show remarkable potential: the rate of primary engraftment was 96% or higher. In addition, the rate of acute GvHD of grade 2 or higher was only 10%, with a similar rate for chronic GvHD.…”

Efficacy and safety of micafungin for prophylaxis of invasive fungal infections in patients undergoing haplo-identical hematopoietic SCT

“…It might be even a first choice, especially in advanced hematological malignancies, because of the presumed stronger graft versus tumor effect related to the partial HLA identity. [1][2][3][4] Haplo-identical Allo-SCT (haplo-SCT) recipients are at high risk for invasive fungal infection (IFI) involving both Candida and Aspergillus species. 5,6 The risk is associated with the degree and duration of neutropenia, the disruption of protective skin and mucosal surface barriers, the GVHD and the use of corticosteroids.…”