Graft-Vs-Leukemia Effects of Allogeneic Stem Cell Transplantation from HLA-Haploidentical Family Members as Compared to HLA-Identical Sibling Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3009-3009
Author(s):  
Hans Jochem Kolb ◽  
Iris Bigalke ◽  
Dominik Termeer ◽  
Susanne Fritsch ◽  
Wolfgang Hill ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Category ◽  
Haploidentical Transplantation ◽  
Conditioning Treatment

Abstract Allogeneic stem cell transplantation produces a strong graft-versus-leukemia effect which may be enhanced by HLA-mismatches and immune recognition as a result of pregnancy. Therefore we compared the results of HLA-haploidentical transplantation (N=113) to those of HLA-identical sibling (N=195) transplantation performed in the same time. Cases were matched by disease category (acute myeloid leukemia-myelodysplastic syndromes, AML/MDS, acute lymphoid leukemia ALL and lymphoma-chronic lymphocytic leukemia NHL/CLL) and stage of the disease (early, intermediate and advanced). HLA-haploidentical transplants were performed with unmodified bone marrow followed by CD6-depleted mobilized blood stem cells on day 6.; patients with leukemia were in more advanced disease in leukemia, they were younger and more often male. In multivariate analysis survival was influenced by HLA-mismatch, stage of the disease and age of the patient, but conditioning treatment and CMV-seropositivity had no significant effect. Transplant related mortality was influenced by the age of the patient and HLA-match, to a lesser extent by the disease category and the stage, whereas CMV-seropositivity and conditioning had no influence. Remission duration was dependent on the stage of the disease, the donor recipient gender combination and the conditioning treatment in univariate analysis; in multivariate analysis only CMV-seropositivity had a poor prognostic impact. In comparable disease stages the relapse rate was not different in HLA-haploidentical from HLA-identical transplantation as was the rate of acute GVHD. In contrast the rate of chronic GVHD was lower in HLA-haploidentical transplantation. In ALL, relapse rate and remission duration was inferior with non-myeloablative conditioning as compared to myeloablative total body irradiation. In HLA-haploidentical transplantation the response rate of leukemia was better in patients homozygous for the cross reactive HLA-C group given a transplant from a heterozygous donor suggestive of NK activity. This GVL activity was not associated with GVH activity. Similarly maternal donors were superior to paternal donors and female donors in male recipients better than other gender combinations for the control of leukemia without increased GVHD. Non-inherited maternal antigen (NIMA) and inherited paternal antigen (IPA) in the graft-vs-host direction had a weak influence on the relapse rate, but no influence on GVHD. On an observational basis several sons and daughters transplanted with stem cells from the mother had a strong GVL effect without any signs of GVHD. However two have been lost due to untreatable pulmonary complications. Donors with cytotoxic antibodies have been excluded from donation, but cellular reactivity will have to be assessed in more detail. Recent progress in controlling EBV-associated disease by selection of donor T cells without expansion will improve HLA-haploidentical transplantation and show the way to selecting donor with the appropriate immune repertoire including reactivity to leukemia.

Hyperlipidemia After Allogeneic Stem Cell Transplantation: Prevalence, Risk Factors and Impact on Prognosis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3458-3458
Author(s):  
Yuki Kagoya ◽  
Sachiko Seo ◽  
Yasuhito Nannya ◽  
Mineo Kurokawa
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Calcineurin Inhibitors

Abstract Abstract 3458 Introduction: Hyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft-versus host disease (GVHD) or calcineurin inhibitors has been considered to be one of the etiologies, its prevalence, risk factors, and the impact on prognosis have not been investigated well. Methods: We performed a retrospective analysis of 194 adult patients who underwent allogeneic SCT between 1995 and 2008 in our institute, and survived more than 100 days after SCT. Hypercholesterolemia or hypertriglyceridemia was defined as more than 240 mg/dl or 200 mg/dl, respectively, at two successive tests at least one week apart after the first 100 days after SCT. Cumulative incidence of hypercholesterolemia or hypertriglyceridemia was analyzed. The time to the development of hypercholesterolemia or hypertriglyceridemia was calculated and the multivariate analysis of pre- and posttransplant variables was performed by a Cox proportional hazards model. Chonic GVHD, chronic liver dysfunction (CLD; defined as more than twice the upper limit of normal for aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, or total bilirubin >3 mg/dl over 3 months) and administration of calcineurin inhibitors were studied as posttransplant factors, which were assessed as time-dependent variables. To analyze the prognosis of patients who developed persistent hyperlipidemia, the multivariate analysis of overall survival (OS), relapse rate, and non-relapse mortality (NRM) was carried out by a landmark approach. Persistent hyperlipidemia was defined as hypercholesterolemia or hypertriglyceridemia continuing more than 3 months. Results: Overall, 83 (42.8%) and 98 (50.5%) patients developed hypercholesterolemia and hypertriglyceridemia, respectively. The median follow-up period of serum cholesterol and triglyceride values in surviving patients was 44 months. The cumulative incidence of each abnormality at 3 years after SCT was 38.1% (95% confidence interval [CI]: 31.0–45.1%), and 46.0% (95% CI: 38.8–52.9%), respectively. In a multivariate analysis, the development of chronic GVHD was independently associated with both hypercholesterolemia (hazard ratio [HR] 2.05, 95% CI: 1.23–3.43, P<0.01) and hypertriglyceridemia (HR 2.04, 95% CI: 1.30–3.18, P<0.01). Besides, CLD was significantly associated with hypercholesterolemia (HR 2.20, 95% CI: 1.39–2.50, P<0.01). Administration of calcineurin inhibitors was not an independent risk factor for the development of hypercholesterolemia (HR 1.23, 95% CI: 0.73–2.08, P=0.43) or hypertriglyceridemia (HR 1.03, 95% CI: 0.61–1.54, P=0.89). Among pretransplant factors, prior hypercholesterolemia and hypertriglyceridemia were associated with posttransplant hypercholesterolemia (HR 2.76, 95% CI: 1.07–7.17, P=0.04) and hypertriglyceridemia (HR 2.04, 95% CI: 1.27–3.27, P<0.01), respectively. Persistent hyperlipidemia was found in 49 patients (25.3%), of which 35 patients (71.4%) developed hyperlipidemia within one year. The median interval to the occurrence of hyperlipidemia of the patients was 180 days after SCT. In univariate analysis, patients with persistent hyperlipidemia had a tendency of better 3-year OS (77.3% vs 64.7%, P=0.23). Multivariate analysis showed that the development of persistent hyperlipidemia was independently associated with better OS (HR: 0.49, P=0.049). Further, although not statistically significant, patients with persistent hyperlipidemia had a tendency of lower 3-year cumulative relapse rate (15.7% vs 20.3%). There were no significant differences in 3-year NRM between patients with or without hyperlipidemia (12.3% vs 13.9%). Conclusions: Both hypercholesterolemia and hypertriglyceridemia are very common complications after SCT. Patients with persistent hyperlipidemia, however, have significantly better OS. Considering a strong association between the development of hyperlipidemia and chronic GVHD, and a tendency of lower relapse rate in patients with persistent hyperlipidemia, hyperlipidemia is regarded as one of the symptoms accompanied with chronic GVHD. Unless severe, its incidence indicates a better control of the primary disease and an improved prognosis. Disclosures: No relevant conflicts of interest to declare.

Extramedullary leukemia relapse after allogeneic stem cell transplantation: a novel mechanism of immune escape?

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 635-640
Author(s):  
Konstantinos Gkirkas ◽  
Maria Stamouli ◽  
Angeliki Karagiannidou ◽  
Spyros Chondropoulos ◽  
Panagiotis Tsirigotis
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Leukemic Cells ◽  
Graft Versus Host ◽  
Haploidentical Transplantation ◽  
Leukemia Relapse

Background: Relapse is a significant cause of treatment failure after allogeneic stem cell transplantation. In many cases relapse occurs when leukemic cells escape from immune surveillance. Methods & results: In the setting of haploidentical transplantation, immune escape is usually the result of the loss of the mismatched haplotype from leukemic cells, while downregulation of HLA-expression has been postulated as a significant cause of immune escape after transplantation with the use of HLA-matched donors. We observed that patients with acute leukemia who relapse at the time of active graft-versus-host-disease, usually develop extramedullary leukemia while they remain free of leukemia in peripheral blood and bone marrow. Conclusion: Our observation points toward a novel mechanism of immune escape which is microenvironment-specific.

Allogeneic Stem Cell Transplantation in Angioimmunoblastic T-Cell Lymphoma (AITL): A Retrospective Survey from the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3042-3042
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
G. Taghipour ◽  
J. Finke ◽  
H. Kolb ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma

Abstract AITL is a rare peripheral T-cell lymphoma characterised by an aggressive behaviour, which primarily affects the elderly. Chemotherapy regimens fail to alter the high relapse rate and overall survival hardly exceeds 25% at 5 years. To date, there is no information on the potential role of allogeneic stem cell transplantation (allo-SCT) in the management of AITL. We report the outcome of 39 patients with a median age of 47 years (24–68), who underwent an allo-SCT between 1995 and 2004 for AITL, and were reported to the EBMT registry. The median time from diagnosis to transplant was 10 months (4–72). Thirty-four patients (87%) had previously received two or more treatment lines, and 16 patients (41%) a previous autologous SCT. Fifteen patients (38%) had a primary refractory disease, 13 (33%) were transplanted in partial remission and the remaining patients were in complete remission (CR) (mostly in 2nd and 3rd CR). Twenty-four patients were transplanted from an HLA-identical sibling and 15 from a matched unrelated donor. A myeloablative conditioning regimen (MAC) was used in 21 patients (cyclophosphamide + total body irradiation in 14), while 18 patients received fludarabine-based reduced intensity conditionings (RIC). Peripheral blood was the source of stem cells in 35 patients (90%). Three patients failed to engraft (one patient in the RIC group). Twenty-one patients (54%) developed acute graft versus host disease (grade I-II, n=16; grade III-IV, n=5). Twenty-eight patients (72%) achieved a CR after the allogeneic procedure. Nine patients died from transplant related mortality (TRM) and 5 patients from disease progression. The cumulative incidence of TRM at 12 months was 19% for the MAC and 26% for the RIC group. After a median follow-up for the surviving patients of 20 months (6–74), 25 patients are alive. Relapse rates at 1 and 3 years were estimated at 10% and 18% for the MAC and 16 and 20% for the RIC patients. Progression free survival rates at 3 years were 67% and 50% and the overall survival at the same time 71% and 56% for the MAC and RIC group of patients, respectively. Although follow up is rather short, these data suggest that allo-SCT results in good overall response and is associated with a low relapse rate in this group of poor risk heavily pre-treated and rather elderly group of AITL patients. Allo-SCT could be considered a therapeutic option for eligible high-risk AITL patients. Nevertheless, the impact of this approach should be further explored in prospective collaborative studies.

Haploidentical Allogeneic Hematopoietic Cell Transplantation as Salvage Therapy for Engraftment Failure After Unrelated and Autologous Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4529-4529
Author(s):  
Yamin Tan ◽  
Huarui Fu ◽  
Yi Luo ◽  
Xiujin Ye ◽  
Li Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Bone Marrow Examination ◽  
Pcr Analysis ◽  
Unrelated Donor ◽  
Haploidentical Transplantation ◽  
Engraftment Failure

Abstract Abstract 4529 Engraftment failure is a rare but life-threatening complication of hematopoietic stem cell transplantation. The treatment of this condition is often challenging. We firstly reported haploidentical donor stem cells transplantation resulted in hematological reconstitution and long-time disease-free survival in a patient who developed engraftment failure after unrelated donor allogeneic stem cell transplantation and failure rescue treatment by re-infusion of autologous “back-up” stem cells. The 39-years-old male patient with acute myeloid leukemia(AML)-M2a achieved complete remission (CR) after one course of induction chemotherapy. He entered a lasting CR with 7 courses post-remission consolidation therapy and decided to receive unrelated donor allogeniec stem cell transplantation. In case of engraftment failure after allo-HSCT, autologous “back-up” cells were harvested after the last course chemotherapy (IDA 15 mg on days 1–2, 10 mg on day 3, Ara-c 300 mg on days 1–3, 200 mg on day 4), and mobilized with G-CSF 5 mg/kg/day for 5 days. The “back-up” cells consisting of 9.94×106/kg CD34+ cells were cryopreservated in liquid nitrogen. Fifteen months after de novo AML, the patient received a myeloablative conditioning regimen of busulfan and cyclophosphamide (busulfan 3.2 mg/kg/day on days -7 to -4, and cyclophosphamide 60 mg/kg/day on days -3 to -2), and an infusion of unrelated allogeneic peripheral stem cells from the Chinese Marrow Donor Program with a HLA-Cw allele mismatch on day 0. The graft contained 11.07×108/kg nucleated cells and 6.35×106/kg CD34+ cells. Pancytopenia was continuously observed during 28 days after transplantation and short tandem repeat-polymerase chain reaction (STR-PCR) analysis showed no donor chimera. As a rescue attempt for graft failure, cryopreservated autologous cells were re-infused on day +28. Unfortunately, pancytopenia was still continuously observed during 23 days after re-infused of “back-up” cells(51 days after unrelated transplantation), and bone marrow examination revealed severe bone marrow hypoplasia. On day +57 and +58 after unrelated transplantation, bone marrow cells containing 2.1×106/kg CD34+ stem cells and peripheral blood cells containing 2.81×106/kg CD34+ stem cells from a haploidentical donor sister (HLA matched in 5/10 alleles by high-resolution genotyping) were infused respectively after reduced-intensity conditioning with fludarabine and ATG (fludarabine 30mg/m2/d on day -5 to -1, ATG 100mg/d on day -4 to -1). Absolute neutrophil count >0.5×109/L was documented on day 12 after haploidentical transplantation. He achieved platelets count >20×109/L on day 28 after haploidentical transplantation. Twenty-nine days after haploidentical transplantation, bone marrow examination showed reconstitution and STR-PCR analysis indicated complete donor chimera. No grades III -IV aGVHD, extensive chronic GVHD, and severe infection after transplantation were observed. Recurrent bone marrow aspiration examinations showed the patient had been in CR. The patient remained alive during a 18-month follow-up after haploidentical transplantation. Our experience suggests that combined haploidentical donor BM and PBSC transplantation after Flu- and ATG-based conditioning could provide an effective therapeutic strategy for engraftment failure after unrelated allo-HSCT in adult patients. Considering the accessibility of haploidentical donors, haploidentical transplantation has the potential to act as a first-line choice for salvage therapy. Disclosures: No relevant conflicts of interest to declare.

Impact of donor source on allogeneic stem cell transplantation for Philadelphia chromosome-negative acute lymphoblastic leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6533-6533
Author(s):  
Satoshi Nishiwaki ◽  
Koichi Miyamura ◽  
Kazuteru Ohashi ◽  
Mineo Kurokawa ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
The Impact ◽  
Donor Source

6533 Background: Although allogeneic stem cell transplantation (allo-SCT) could improve the outcome of adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source, particularly the position of cord blood (CB) transplantation, is still uncertain. Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients transplanted at the first time between 1998 and 2009 with myeloablative preparative regimens who were registered in the Japan Society for Hematopoietic Cell Transplantation database. Two hundred and thirty-three received CB transplantation [first complete remission (CR1): 95, subsequent CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor (URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR: 207). Results: Overall survival (OS) in patients after CB transplantation in CR1 was comparable with that after allo-SCT from URD or RD [57% in CB, 64% in URD, and 65% in RD at 4 years, respectively, P=0.11]. Donor source was not a significant risk factor for OS in multivariate analysis. Although URD was a favorable factor for relapse and an unfavorable factor for non-relapse mortality (NRM), CB was not a significant factor for them [Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively (P=0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years, respectively (P=0.0001)]. Among CB recipients in CR1, age at allo-SCT (45 years or older) was solely a significant adverse prognostic factor in multivariate analysis. Among patients younger than 45 years who received allo-SCT in CR1, OS after CB transplantation was significantly better than that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%, P=0.04). Similarly, OS was not different by donor source in subsequent CR or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD, P=0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P=0.20 at 4 years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes as either RD or URD in any disease status. CB transplantation is a good alternative for adult Ph(-) ALL patients without a suitable RD or URD.

Total Lymphocyte and Natural Killer (NK) Cell Count Day 30 Post-Transplant Strongly Predict Transplant Outcome after T Cell Depleted Allogeneic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2993-2993
Author(s):  
Bipin N. Savani ◽  
Stephan Mielke ◽  
Katayoun Rezvani ◽  
Agnes Yong ◽  
Nancy Hensel ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Count ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Nk Cell ◽  
Transplant Outcome ◽  
Post Transplant

Abstract One hundred and fifty-seven patients with leukemia (80 CML, 48 AML/MDS, 29 ALL) received a T cell depleted myeloablative allogeneic stem cell transplantation (SCT) from an HLA-matched sibling between 09/1993–09/2005. Conditioning consisted of TBI (12–13.6 Gy) + cyclophosphamide (96) or cyclophosphamide and fludarabine (61). The stem cell source was G-CSF mobilized peripheral blood stem cell (PBSC) in 129 and bone marrow in 28 patients. T cell dose with graft ranged from 0.2 – 2 × 105/kg CD3+ cells. GVHD prophylaxis was with low dose cyclosporine (level 100–200 ng/ml) in 103 and standard dose in 54. Patients without ≥ grade II acute GVHD received 1–2 donor lymphocyte infusion of 107 CD3+ cells/kg between days 45 and 100. Absolute lymphocytes on day 30 (LC30) was available in 154 patients (3 patients died before day 30) and 54 day +30 post-transplant samples were available for lymphocyte subset analysis. Median lymphocyte count on day +30 (LC30) was 400/μl, (range 10–3295) and 150/μl, (range 6–1005) for CD56+, CD16+ CD3− NK cells (NK30). Statistical analysis was performed on SPSS14 software. Median age of the group was 34 years (range 10–56). 78 patients had standard risk (SR) disease in first remission or first chronic phase of CML. The remaining 79 had high risk (HR) disease. At the time of analysis 85 patients are (51.5±4%) are alive with median follow-up of surviving patients 1392 days (range 147–4208). Only 9 patients (3 above median LC30) developed aGVHD before day+30. Patients with ≥ median LC30 had significantly better transplant outcome: survival 71±5 vs. 36 ±5.5%, p<0.0001; DFS 71±5 vs. 31±5 %, p<0.0001; NRM 10±3.5 vs. 38 ±6%, p<0.0001; relapse 22±5 vs. 51±7.5%, p=0.004; ≥ II aGVHD 34 ±5 vs. 51±6%, p=0.05. In multivariate analysis only disease risk and LC30 emerged as independent prognostic factors: LC30 above 400/μl was associated with improved survival (RR 4.3), DFS (RR 4.5), less relapse (RR 10.3), NRM (RR 3.3) and aGVHD (RR 2.3). LC30 impacted on outcome of both HR and SR disease groups (Figure). LC30 and NK30 were highly correlated (r2– 0.45, p<0.0001) and NK30 above 150/μl was also associated with improved transplant outcome: In multivariate analysis of this subset of 54 patients, SR disease and NK30 emerged as the only independent factors with better outcome for NK30 >150/μl: higher survival (RR 3), and DFS (RR 3), less relapse (RR 4.8), less NRM (RR 3) and less aGVHD (RR 5.3). This study does not define whether LC30 is a surrogate for NK cell count or whether both are a surrogate for some other undetected prognostic factor. However the inverse relationship between NK count and aGVHD suggests an NK-mediated effect through elimination of host antigen presenting cells as has been described in mismatched SCT but also in HLA identical SCT by Cook et al (Blood2004, 103, 1521) Prospective studies to correlate transplant outcome with NK cell recovery and function after HLA identical SCT are indicated. Figure Figure

The Outcome of Allogeneic Stem Cell Transplantation in Chronic Lymphocytic Leukaemia: A Single Centre 10-Year-Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4515-4515
Author(s):  
Patrycja Zielinska ◽  
Malgorzata Krawczyk-Kulis ◽  
Miroslaw Markiewicz ◽  
Monika Dzierzak-Mietla ◽  
Anna Koclega ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Cumulative Probability

Abstract Abstract 4515 Chronic lymphocytic leukemia (CLL) is an incurable disease when treated with standard chemotherapy. The only possibility to provide cure is allogeneic stem cell transplantation (allo-SCT). CLL patients aged less than 55 account for about 15% of patients and these cases allo-SCT should be taken into consideration. The indications for allo-SCT are as follows: del17p, resistance to chemoimmunotherapy, Richter’s syndrome or recurrent disease. A retrospective analysis of allo-SCT in 18 patients (10 males, 8 females) with CLL transplanted in years 2000–2010 was performed. The aim of the study was to assess of long term follow-up outcome of allo-SCT in CLL patients. The median age at diagnosis was 41ys (range: 35–51). The sibling donor was available in 16 cases (2 pts were mismatched), unrelated donors were in 2 cases (1 mismatched). Most of the pts (16 out of 18) were MRD positive when allotransplanted. Median lymphocytosis preceeding allo-SCT was 5.9G/l. Peripheral blood was the source of stem cells in 9 cases (50%), and bone marrow in the remaining 9 cases, 2 pts were transplanted with stem cells from bone marrow and peripheral blood. 4 pts (22%) underwent the allograft procedure twice or more. Reduced intensity conditioning with alemtuzumab was performed in 9 pts (50%), myeloablative regimen in 4 cases and RIC with rituximab in one case.The median number of CD34+cellsx10^6/kg was 4.1 (range: 0.86–9.64). All but one patient engrafted (this pt was transplanted again successfully in one year time). Acute graft-versus host disease (GvHD) was noted in 46% of pts (only in 2 pts grade IV). Extensive GvHD was observed only in 2 pts. Donor lymphocyte infusion (DLI) was performed in 8 pts (44%). With a median follow-up of 73 months (range: 9–89) for surviving patients, the five-year Kaplan-Meier of overall survival (OS) and progression free survival (PFS) was 55,5% and 34%, respectively. At five years, the cumulative probability of non-relapse mortality was 15%. Allogeneic stem cell transplantation remains the effective treatment in CLL for selected group of patients. Disclosures: No relevant conflicts of interest to declare.

The Impact of ATG/Alg in Preconditioning On the Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4185-4185
Author(s):  
Koji Kato ◽  
Yoshiko Atsuta ◽  
Kazuteru Ohashi ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Sources ◽  
The Impact

Abstract Abstract 4185 Background: Since the clinical implication of anti-lymphocyte globulin (ATG/ALG) in allogeneic stem cell transplantation (allo-SCT) is not fully understood, we tried to identify the clinical impact of ATG/ALG in patients with acute leukemia who received allo-SCT in Japan. Patients and Methods: We analyzed patients with ALL (n=5494) and AML (n=8115) who received first allogeneic SCT from 1983 to 2009 with (n=356) or without (n=13253) ATG/ALG. Their stem cell sources were bone marrow (BM, n=9056), peripheral blood (PB, n=1918), and cord blood (CB, n=2575) and they were transplanted at 1st complete remission (CR1, n=5681), 2nd CR (CR2, n=2495), and advanced stages (>CR3, n=5033). Results: Five year overall survival (5y OS) of all patients with or without ATG/ALG was 33.6% vs 44.5%, respectively (P<0.001) and multivariate analysis showed that ATG/ALG significantly reduced acute GVHD (P<0.001, HR=1.980) as well as chronic GVHD (P<0.001, HR=1.894). According to stem cell sources, 5y OS with or without ATG/ALG was 35.8% vs 47.5% (P<0.001) in BM, 34.7% vs 37.6% (P=0.067) in PB and 18.3% vs 39.9% (P<0.001) in CB. By multivariate analysis, ATG/ALG significantly reduced A-GVHD (P=0.005, HR=1.565) but decreased OS (P=0.004, HR=0.729) in BM, it reduced A-GVHD (P<0.001, HR=2.376) and C-GVHD (P<0.001, HR=2.691) but lowered engraftment (P=0.046, HR=0.810) in PB, and it increased TRM (P=0.004, HR=0.437) with decreased OS (P=0.011, HR=0.576) in CB. In Haplo transplantation (SCT from 2 or 3 antigens of HLA mismatched family donor, n=337), multivariate analysis showed that ATG/ALG did not affect the relapse, TRM and OS but, it significantly lowered engraftment (P=0.002, HR=0.602), and reduced A-GVHD (P<0.001, HR=2.622) as well as C-GVHD (P<0.001, HR=3.834). In contrast to these results, ATG/ALG did not affect the relapse rate irrespective of stem cell source or diagnosis. Conclusion: In allogeneic stem cell transplantation for patients with ALL and AML, ATG/ALG contribute in reducing acute and chronic GVHD without affecting relapse rates but it was a risk factor of OS for patients who received BM or CB. Disclosures: No relevant conflicts of interest to declare.

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