Allogeneic stem cell transplant for chronic myeloid leukemia as a still promising option in the era of the new target therapy.

BACKGROUND/AIM: Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell transplant (SCT) in CML treatment--as a former "nearly monopolistic" therapeutic manner--is nowadays controversial. The objective of this retrospective study was to evaluate the results obtained in the treatment of CML patients, with a particular attempt to define parameters critical for clinical benefit and superior overall outcome following allogeneic SCT. METHODS: A total of 32 CML patients (27 in chronic phase and 5 with advanced disease), with female/male ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN-alpha) with or without ARA-C, and additional 7 patients with no response to imatinib mesylat (IM). The time from diagnosis to SCT was approximately 12 (range 3-37) months. The patient were categorized according to the risk for the disease, transplant-related mortality (TRM) scoring system, and stem cell (SC) source. The basic conditioning regimen was a combination of busulphan and cyclophosphamide (BuCy-2). Graft-versus-host disease (GvHD) was typically prevented with cyclosporine-A (CsA) and methotrexate (MTX). RESULTS: Engraftment was observed in 26 (84.4%) patients, with polymorphonuclear (PMNs) and platelet (Plt) recovery on the 15th (range 10-22) and 19th (range 11-29) posttranspalnt days, respectively. Acute GvHD (aGvHD) had 13/26 (50%), and chronic GvHD (cGvHD) 10/21 (47.1%) patients. The incidence of overall TRM was 46.8% (15/32), while early death was noticed in 4 (12.5%) patients. A cause of death in 9 (28.1%) patients was cGvHD, in 2 (6.25%) patients infection, and in 3 (9.35%) cases disease-relapse was occurred. Fourteen (43.7%) of the patients are still alive, 9 from the low-risk group for TRM, with long-term survival from 1 to 16 years. Patients who received SCs from peripheral blood (PB) vs bone marrow (BM) had significantly faster engraftment (p < 0.05), lower oropharingeal mucositis rate (25% vs 70%; p < 0.05), but more frequent cGvHD (83.3% vs 30.3%; p < 0.05). A significantly improved (log-rank = 2.39; p < 0.01) overall survival (OS) was obtained in BM-setting. CONCLUSION: The results obtained in this study are in accordance with data from analogous clinical trials. Exactly, in the era of the new target therapy (TKI application), allogeneic SCT can be still a convenient therapeutic approach for well-selected CML-patients, especially for those with initial high-risk disease and lower probability of TRM.

Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies.

BACKGROUND/AIM: Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease--aGvHD) and delayed (chronic GvHD--cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). METHODS: We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML)--39, acute lymphoblastic leukemia (ALL) 47, chronic myeloid leukemia (CML)--32, myelodysplastic syndrome (MDS)--10, Hodgkin's lymphoma (HL)- 2, multiple myeloma (MM) 3, granulocytic sarcoma (GrSa) 3, severe aplastic anemia (sAA)--22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one "Large Volume Leukapheresis" (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 microg/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (P < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT hd a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the long-term OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.