HLA Mismatch Allogeneic Blood and Marrow Transplantation / 대한내과학회지

A full haplotype mismatch or mismatched unrelated donor transplantation nowadays are well being focused on, as main alternative donor tools for acute leukemia patients in desperate need of allogeneic blood and marrow transplantation (BMT), the ability to overcome various posttransplant complications by adopting the T-cell replete technique in reality. Increasing numbers of allogeneic BMT in good clinical status are largely because it's the best post-remission therapy especially for many patients with acute leukemias. Due to the problems of unavailable donors at appropriate clinical condition and the process of long duration of donor searching step with relatively much higher cost, some of physicians have indulged in haploidentical BMT rather than mismatched unrelated BMT. Both myeloablative and reduced intensity conditioning regimens for mismatched BMT with T-cell replete or T-cell depletion method have been exploited worldwide. Most of all, Asian countries have experienced lower rates of severe acute and chronic GvHD, graft failure, and impressively low transplant-related mortality with longer follow-up duration. Also, we need many future trials to compare outcomes between these two transplant modalities with cord blood transplant in various diseased patient populations.

Megadose CD34+ Hemopoietic Stem Cell Transplantation for Patients with High Risk Acute Myeloid Leukemia Who Have No HLA Matched Donor: A Pilot Study of a Full Haplotype Mismatch Transplantation

BACKGROUND: Haploidentical transplantation has become a popular modality of treatment for acute myeloid leukemia (AML) patients lacking donors with matching HLA. We attempted to assess the success rate and ramifications of full haplotype mismatch transplantation. METHODS: Four patients received stem cell transplantation from their full haplotype mismatched family donors. The conditioning regimen included total-body irradiation, intravenous busulfan, antithymocyte globulin, and fludarabine. Megadose CD34+ stem cell transplants were performed, in a dosage range between 10.9 X 10 (6) /kg and 20.6 X 10 (6) /kg. Neither GvHD prophylaxis nor post-transplant G-CSF were administered. We monitored patients' bone marrow cellularity and peripheral blood chimerism using real-time PCR. RESULTS: All patients evidenced stable engraftment. The most frequent side effect was severe mucositis, but all patients recovered successfully, without early death. No patients exhibited acute GvHD. Two refractory patients relapsed soon after transplantation. The other 2 patients have remained in good clinical condition, with a follow-up duration of 1~4 months. CONCLUSION: Using a newly-developed conditioning regimen, we were able to circumvent GvHD and graft failure, which are the main limitations associated with full haplotype mismatch transplantation. According to our analysis of the relevant literature, it appears that this is the first report of such a conditioning regimen.

Megadose CD34+ hemopoietic stem cell transplantation for patients with high risk acute myeloid leukemia who have no HLA matched donor: A pilot study of a full haplotype mismatch transplantation / 대한내과학회지

BACKGROUND: Haploidentical transplantation has become a considerable clinical choice for acute myeloid leukemia (AML) patients lacking a HLA matched donor. We tried to reveal the possible role of a full haplotype mismatch transplantation. METHODS: Four patients received stem cell transplantation from their full haplotype mismatched family donors. Conditioning regimen included total-body irradiation, intravenous busulfan, antithymocyte globulin, and fludarabine. Megadose transplants of CD34+ stem cells were in the range of 10.9 x 106/kg and 20.6 x 106/kg. Neither GvHD prophylaxis nor post-transplant G-CSF were given. We monitored patients' bone marrow cellularity and chimerism in the peripheral blood using real time PCR. RESULTS: All patients showed stable engraftment. The most frequent side effect was severe mucositis, but all patients recovered successfully without early death. Nobody showed acute GvHD. Two refractory patients were relapsed early after transplantation. Other 2 patients have been in good clinical condition with follow-up duration of 1~4 months. CONCLSUION: We could overcome the main limitations-a GvHD and a graft failure- of a full haplotype mismatch transplantation with a newly developed conditioning regimen that might be used firstly according to review of literature. Although our study sample numbers and duration of follow-up are not enough yet, at least in patients who were in complete remission and categorized as high-risk AML, we suggest that this treatment modality should be considered actively.

Haplotype Mismatch Transplantation using High-dose CD34+ Cells with Stratified New Conditioning Regimens in Patients with Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: Although haploidentical transplantation has become a clinical reality for acute myeloid leukemia (AML) patients lacking a HLA compatible donor due to several encouraging reports, it is still considered as one of an experimental treatment modalities. METHODS: Eleven patients received stem cell transplantation from family donors having mismatched HLA haplotypes. For patients who were planned for 2 or 3 major antigens mismatch transplantation, their conditioning regimens included total-body irradiation (TBI), intravenous busulfan, antithymocyte globulin, and fludarabine in 6 patients and non-TBI containing regimen in 2 patients. For 3 patients with 1 major antigen mismatch sibling donor, we used 3 different regimens according to the patients' condition. The median number of infused CD34+ cells were 15.4x10(6)/kg (range, 8~21.2). RESULTS: Ten patients who were followed up for at least median 4 months (range, 17 days-15 months) showed stable engraftment. Patients who received haploidentical transplantation in first or second complete remission (CR), all showed continuous CR within our study period and showed no acute graft-versus-host disease or transplant-related mortality during 100 day posttransplant. Three of 5 patients who were in relapse or refractory state finally died in relapse. Two of 3 patients who received the full haplotype mismatch transplantation in CR died after 4 months posttransplant due to critical infections associated with delayed immune recovery. CONCLUSION: Our experience suggests that haploidentical transplantation is at least, in part, feasible or desperate treatment for patients with high-risk AML in CR. We need further stable plan to enhance the immune recovery for these patients as soon as possible.