Unrelated Donor Hematopoietic Stem Cell Transplantation for High-Risk Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5407-5407
Author(s):  
De Pei Wu ◽  
Xiaowen Tang ◽  
Aining Sun ◽  
Zheng-zheng Fu ◽  
Huiying Qiu
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Mixed Chimerism ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Donor Chimerism

Abstract objective: To investigate the efficacy of unrelated donor hematopoietic stem cell transplantation(URD-HSCT) for high-risk leukemia. Methods: From 2001 to March, 2006, 24 patients of high-risk leukemia underwent HSCT with unrelated donor. Patients between 6 and 49 years of age(median age 21.5 years) There were 16 unrelated donor’s grafts came from Buddhist Tzu Chi Stem Cells center in Taiwan, and 8 unrelated grafts came from Red Cross Society of China Hematopoietic Stem Cell Marrow Donor Program Administration Center. Fifteen patients received bone marrow transplantation and another 9 patients received peripheral blood stem cell transplantation. Eighteen patients were fully matched with their donors for HLA loci A and B as well as for HLA-DRB1. Four of 24 patients had 1 molecular loci mismatch and 2 of 24 patients had 2 molecular locus mismatch. The conditioning regimen consisted of modified BU/CY or modified total body irradiation(TBI) plus CY. Eleven patients received cyclosporine (CSA), short-term methotrexate(MTX) and mycophenolate mofetil (MMF) as the regimen of prophylaxis of GVHD. Ten patients received CSA, MTX and MMF plus ATG/ALG for GVHD prophylaxis. The combination of CSA, MTX, MMF,ATG/ALG and CD25 monoclonal antibody for preventing GVHD in 3 patients. Results: The incidence and severity of regimen-related toxicity were mild. The median number of MNC and CD34 positive cell was 4.18×108/kg and 7.75×106/kg respectively. The median time of the engraftment of neutrophil and platelet was 13 days and 19 days posttransplant respectively. The incidence of infection posttransplant was 70%(17/24). The complicated pneumonitis occurred frequently (13/17, 76%), The incidence of grade I-II and grade III-IV acute GVHD was 33% and 41% respectively. Limited chronic GVHD occurred in 25% patients and extensive cGVHD presented in 31% patients. Median follow up was 16 (range 1~57) months after transplantation. 75% patients achieved full donor chimerism(FDC) detected by STR-PCR and FISH. While 25% patients presented mixed chimerism(MC) and 2 of them converted to unstable MC. Decreasing values of donor chimerism were detected prior to the relapse of disease. Furthermore the treatment related mortality(TRM) was 33%(8/24), The incidence of relapse was 8%. Until now 14 patients are still alive. The median overall survival time were 26 months and 5-years expected survival was 47.7%. Conclusion: URD-HSCT can be an effective and curable approach for leukemia with higher incidence of GVHD and infection. The treatment for the severe and deadly GVHD and pulmonary infection are still major problems need to be resolved in the future.

Unrelated Donor Hematopoietic Stem Cell Transplantation for Treatment of High-Risk Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4418-4418
Author(s):  
Wu Depei ◽  
Xiao wen Tang ◽  
Ai ning Sun ◽  
Zheng -zheng Fu ◽  
Miao Miao ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Donor Chimerism

Abstract objective: To investigate the efficacy of unrelated donor hematopoietic stem cell transplantation(URD-HSCT) for high-risk leukemia. Methods: From June 2001 to July 2008, 62 patients of high-risk leukemia underwent HSCT with unrelated donor. The median age was 24(6~49)years. There were 21 unrelated donor’s grafts came from Buddhist Tzu Chi Stem Cells center in Taiwan, and 41 unrelated grafts came from Red Cross Society of China Hematopoietic Stem Cell Marrow Donor Program Administration Center. Seventeen patients received bone marrow transplantation and another 45 patients received peripheral blood stem cell transplantation. Fifty patients were fully matched with their donors for HLA loci A and B as well as for HLA-DRB1. Eight of 62 patients had 1 molecular loci mismatch and 4 of 62 patients had 2 molecular locus mismatch. The conditioning regimen consisted of modified BU/CY or modified total body irradiation(TBI) plus CY. Eleven patients received cyclosporine (CSA), short-term methotrexate (MTX) and mycophenolate mofetil (MMF) as the regimen of prophylaxis of GVHD. Forty |four patients received CSA, MTX and MMF plus ATG/ALG for GVHD prophylaxis. The combination of CSA, MTX, MMF,ATG/ALG and CD25 monoclonal antibody for preventing GVHD in 4 patients. Other two patients received Tacrolimus, short-term MTX and ATG to prevent GVHD. Results: The incidence and severity of regimen-related toxicity were mild. The median number of MNC and CD34 positive cell was 4.48×108/kg and 4.06×106/kg respectively. The median time of the engraftment of neutrophil and platelet was 13 days and 16 days posttransplant respectively. The incidence of infection posttransplant was 48%. The complicated pneumonitis occurred frequently (67%), The incidence of grade I–II and grade III–IV acute GVHD was 17% and 23% respectively. Limited chronic GVHD occurred in 17% patients and extensive cGVHD presented in 14% patients. Median follow up was 6 (range 1 `85) months after transplantation. 83% patients achieved full donor chimerism(FDC) detected by STR-PCR and FISH. While 17% patients presented mixed chimerism (MC) and 10 of them converted to unstable MC. Among them 4 patients presented graft rejection and 6 patients suffered from relapse. Decreasing values of donor chimerism were detected prior to the relapse of disease. Furthermore the treatment related mortality (TRM) was 16%(10/62), The incidence of relapse was 10%. Until now 37 patients are still alive. The 5-years expected survival was 52.2%. Conclusion: URD-HSCT can be an effective and curable approach for high risk leukemia with higher incidence of GVHD and infection. The treatment for the severe and deadly GVHD and pulmonary infection are still major problems need to be resolved in the future.

Impact of Cytogenetics on Outcome of Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for Adults with AML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 830-830 ◽  
Author(s):  
Martin Tallman ◽  
Gordon Dewald ◽  
Hillard Lazarus ◽  
Sharavi Gandham ◽  
Gene Nelson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Kaplan Meier

Abstract Matched unrelated donor hematopoietic stem cell transplantation (MUD HSCT) is a potentially curative treatment for patients with acute myeloid leukemia (AML). The graft-versus-leukemia (GVL) effect may be potent enough to overcome the otherwise poor prognosis associated with AML though its efficacy for high risk cytogenetic subgroups is uncertain. To test this hypothesis, we analyzed outcomes by cytogenetic risk group in 324 patients in first complete remission (CR1), and 440 in CR2 undergoing NMDP-facilitated MUD HSCT between 1988–2002. Using the SWOG/ECOG classification of cytogenetic risk groups (Slovak et al. Blood, 2000) cytogenetics were classified as favorable in 14% of patients, intermediate in 71% and unfavorable in 16%. 56% of the patients were male and 42% were > 35 years at HSCT. 76% of patients and donors were matched at HLA-A, -B and -DRB1, 17% were mismatched at one or more loci and 7% were potentially matched (serologically matched at HLA-A and -B and potentially allele matched at -DR). Disease Status N Kaplan-Meier Estimate for Survival at 5 years Kaplan-Meier Estimate for Disease-Free Survival at 5 years Cumulative Incidence for 100 Day Transplant-Related Mortality Cumulative Incidence for Relapse at 5 years * p-value indeterminate; ** p=0.01 CR1 324 32 ± 6% 32 ± 5% 32 ± 5% 18 ± 4%     Intermediate 227 33 ± 7% 32 ± 7% 31 ± 6% 16 ± 5%*     Unfavorable 85 31 ± 11% 31 ± 10% 29 ± 10% 23 ± 9%* CR2 440 36 ± 5% 35 ± 5% 25 ± 4% 16 ± 3%     Favorable 93 46 ± 10% 44 ± 10% 25 ± 9% 10 ± 6%**     Intermediate 313 33 ± 6% 32 ± 5% 27 ± 5% 16 ± 4%**     Unfavorable 34 37 ± 17% 38 ± 16% 15 ± 12% 32 ± 15%** These data suggest that with the exception of the 5-year relapse rate, results of cytogenetics have little apparent influence on the outcome for patients undergoing MUD HSCT for AML in CR1. In CR2, results in patients with favorable cytogenetics appear to be better than those with intermediate or unfavorable cytogenetics, but are not statistically significantly different. Effective GVL and protection against relapse is observed, even in high risk cytogenetic subgroups. In this retrospective study, other prognostic factors may influence the outcome, but overall survival for patients with unfavorable cytogenetics appears at least as good as previously reported for matched sibling HSCT.

Preemptive Management of Epstein-Barr Virus Reactivation after Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5000-5000
Author(s):  
Imran Ahmad ◽  
John Kwan ◽  
Nathalie Meuleman ◽  
Philippe Lewalle ◽  
Francoise Crokaert ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Introduction - Epstein-Barr virus (EBV) reactivation after hematopoietic stem cell transplantation can lead to posttransplant lymphoproliferative disease (PTLD), which carries a high mortality rate. Transplants using T-cell-depleted graft or antithymocyte globulin are considered as high-risk. Among therapeutic and prophylactic options being developed, B-cell depletion with monoclonal antibodies is encouraging. Since viral load after transplantation is correlated to PTLD occurrence, we have developed a preemptive attitude based on PCR-guided rituximab administration. Methods - We monitored 115 transplant patients with a quantitative PCR for EBV DNA performed on whole-blood samples. Criteria for treatment initiation were a single PCR above 40,000 DNA genome copies per litre (gCop/L) or two rising values above 10,000 gCop/L. Weekly rituximab infusion at the dose of 375 mg/m2 was administered until negative PCR results were available. We evaluated incidence of EBV reactivation and PTLD development. Results - 19 patients (16.5%) met the criteria for treatment. Incidence of reactivation was the same in high-risk and standard-risk patients (12 vs 7, p=0.38). One patient developed PTLD after discontinuation of therapy due to a serious adverse event. No other serious adverse events were noticed. Viral load disappeared after a median of 3 cycles of therapy and weekly monitoring allowed prompt intervention. No PTLD-related death was observed, all-cause mortality in the treated population was 68%. Conclusions - Our PCR-guided and rituximab-based preemptive approach to avoid PTLD after allogeneic hematopoietic stem cell transplantation is safe and feasible but probably overtreated patients. Prospective trials should concentrate on high-risk patients, use uniform PCR techniques, and consider higher threshold values for treatment initiation. Characteristics of transplant population (n=115) Age (median and range) 39 (15–69) Diagnosis AML : acute myeloid leukemia - ALL : acute lymphoblastic leukemia - NHL : non Hodgkin’s lymphoma - CML : chronic myelogenous leukemia - MM : multiple myeloma - MDS : myelodysplastic syndrome - CLL : chronic lymphocytic leukemia - AA : aplastic anemia - Sib donor : HLA-matched sibling donor - MUD : HLA-matched unrelated donor     AML 31     ALL 17     NHL 15     CML 12     MM 11     MDS 10     CLL 6     AA 4     Others 9 Type of transplant     Myeloablative Sib donor 29     Myeloablative MUD 12     Nonmyeloablative Sib donor 32     Nonmyeloablative MUD 9     Haploidentical 33 Alive 32 (28%) Characteristics of treated patients (n=19) Age (median) 30 (18–62) AML : acute myeloid leukemia - ALL : acute lymphoblastic leukemia - NHL : non Hodgkin’s lymphoma - CML : chronic myelogenous leukemia - MM : multiple myeloma - MDS : myelodysplastic syndrome - CLL : chronic lymphocytic leukemia - AA : aplastic anemia - Sib donor : HLA-matched sibling donor - MUD : HLA-matched unrelated donor - TCD : ex vivo T cell depletion - ATG : antithymocyte globulin administration - D/R : donor / recipient serology - Cnl : calcineurin inhibitor (cyclosporin, tacrolimus) - MMF : mycophenolate mofetil Diagnosis AML 4 ALL 6 NHL 0 CML 4 MM 0 MDS 1 CLL 1 AA 1 Others 2 Type of transplant Myeloablative Sib donor 6 Myeloablative MUD 3 Nonmyeloablative Sib donor 4 Nonmyeloablative MUD 0 Haploidentical 6 TCD/ATG 12 EBV serology D+/R+ 17 D−/R− 0 D+/R− 1 D−/R+ 1 Immunosuppressive drugs Cnl alone 2 steroids alone 1 Cnl-steroids 5 Cnl-MMF-steroids 4 Others 1 None 0 GVHD Acute 9 Chronic 2 Alive 6 (32%) Cause of death relapse of malignancy 4 GVHD 4 Infection 4 Others 1

scholarly journals Induction Treatment and Feasibility of Allogeneic Hematopoietic Stem Cell Transplantation in Young Patients (<65 years) with High-Risk Cytogenetic and Secondary Acute Myeloid Leukemia (AML): A Single Center Experience in Argentina with CLAG-M and 7+3

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5132-5132
Author(s):  
Maria Lucia Fuente ◽  
Maria Del Rosario Custidiano ◽  
Santiago Cranco ◽  
Laura Korin ◽  
Paola Ochoa ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Median Time ◽  
Induction Treatment ◽  
Hematopoietic Stem ◽  
Free Survival

BACKGROUND Patients with adverse cytogenetic or secondary AML (s-AML) have significantly worse outcomes and lower survival rates. In this high risk subgroup of patients, early consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) can improve results, especially in those who achieve negative measurable residual disease (MRD-). More effective treatments than standard 7+3 are needed. CLAG-M is a salvage regimen that has demonstrated high response rates with good tolerance, and seems to be promising in the upfront setting. AIMS To estimate CR and MRD- rates, overall survival (OS) and event free survival (EFS) in transplant eligible patients with high risk AML treated in our center.To compare CR rate and transplant feasibility in CR1 with 7+3 vs. CLAG-M as induction treatment in s-AML. PATIENTS AND METHODS We analyzed adult patients (18-65 years old) with high risk AML (defined by adverse cytogenetic according to ELN2017 or s-AML) who were treated in our institution between 2010 and 2018. All patients were transplant eligible and had an available donor. Clinical information was collected from medical records. We evaluated CR1 and MRD- rates, EFS and OS. We also compared CR rates and HSCT feasibility in s-AML after treatment induction with CLAG-M and 7+3. The survival analysis was estimated with Kaplan-Meier method and the comparison between variables was performed through log-rank test. RESULTS Twenty-one patients were included (13 s-AML and 8 with adverse cytogenetic). The median age at diagnosis was 54 years (21-64); 13 female/8 male. Out of 21 patients, 14 received 7+3 induction and 7 CLAG-M. The median follow-up time was 11 months (0.9-90.8), median EFS and OS for the whole group was 1.05 and 13.5 months, respectively. Two-year OS was 35%. CR1 was achieved in sixteen patients (76%), 10 of them MRD-. The median time to CR1 was 33 days, the median OS of these patients was 26.7 months (figure 1). Eleven patients (52%) were refractory to first induction, 10/14 in the 7+3 subgroup, and only 1/7 patients treated with CLAG-M. Six of them converted to CR after reinduction (5 with CLAG-M). Fourteen (67%) underwent HSCT in CR1. The median time to HSCT consolidation was 106 days. The median relapse free survival in transplanted patients has not been reached (Table 1). Considering only s-AML, 6 patients received 7+3 and 7 CLAG-M. Median age in 7+3 subgroup was 41 vs. 57 years in CLAG-M. The median OS was 13.5 months. In the 7+3 cohort, only 1 achieved CR (16%); the other five received reinduction with CLAG-M, and 4 converted to CR1. The median time to CR1, EFS and OS were 82 days, 1 month and 26 months respectively. In contrast, 4 of the 7 patients (57%) that received CLAG-M achieved CR1, but only 1 of the 3 that were refractory could convert to CR. The median time to CR1 in patients treated with CLAG-M was 27 days, median EFS 7.5 months and median OS has not been reached (Figure 2). There were no statistically significant differences between the two treatment groups. Eight patients (62%) could be bridged to HSCT, 4 of each subgroup (Table 2). CONCLUSIONS Our results in this real life small cohort of high risk AML were similar to historical controls. In the s-AML subgroup, differences between 7+3 and CLAG-M were not statistically significant probably due to the low number of patients analyzed. However, patients who received CLAG-M required less cycles of treatment to achieved CR1, allowing HSCT rapidly in this selected population. Since most of the refractory patients to 7+3 responded to reinduction with CLAG-M, both groups had similar transplant rates. According to our experience CLAG-M might be an attractive treatment option with high CR rates and acceptable safety profile. In this high risk AML population, two thirds of the patients were effectively "bridged" to HSCT with a 2-year OS rate of 35%. Disclosures No relevant conflicts of interest to declare.

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