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

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.

Which Patients with Adult Acute Lymphoblastic Leukemia Should Undergo a Hematopoietic Stem Cell Transplantation? Case-Based Discussion

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 444-452 ◽  
Author(s):  
Hillard M. Lazarus ◽  
Selina Luger
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

AbstractThe decision to proceed to transplant for adult patients with acute lymphoblastic leukemia (ALL) is not clear-cut. Relapse and nonrelapse mortality continue to plague the outcome of hematopoietic stem cell transplantation (HSCT) even when undertaken in complete remission (CR). Those considered to be at high risk for relapse often are considered for HSCT in first complete remission (CR1) while those at lower risk may not be referred until they have relapsed, when their chances for cure are very poor. In some patients who have a suitable histocompatible sibling, disease- or patient-related factors may override the potential benefit of allogeneic HSCT. Because many patients do not have a suitable histocompatible sibling, one has to consider the relative merits of autologous transplantation versus use of an alternative allogeneic stem cell source, such as a matched-unrelated donor (MUD), umbilical cord blood (UCB) donor, or haploidentical donor. Deciding among these options in comparison to chemotherapy even in high-risk patients is difficult. In the review, the risks and benefits of these choices are discussed to determine whether and by what means to proceed to HSCT in adult patients with ALL who are in CR1. Presented are two patients with ALL and a discussion of how the data we provide would lead to a decision about the selection of therapy.

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.

scholarly journals Hematopoietic stem cell transplantation for infants with high-risk KMT2A gene rearranged acute lymphoblastic leukemia

2021 ◽  
Author(s):  
Takayuki Takachi ◽  
Tomoyuki Watanabe ◽  
Takako Miyamura ◽  
Akiko Saito ◽  
Takao Deguchi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Pediatric Leukemia ◽  
Hematopoietic Stem

The role of allogeneic hematopoietic stem cell transplantation (HSCT) for infants with acute lymphoblastic leukemia (ALL) and KMT2A gene rearrangement (KMT2A-r) is controversial in terms of both its efficacy and potential of acute and late toxicities. In the Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10, by introducing intensive chemotherapy, indication of HSCT was restricted to the patients with high-risk (HR) features only (KMT2A-r and either age <180 days or presence of central nervous system leukemia). Of the 56 HR patients, 49 achieved complete remission. Forty-three patients received HSCT in first remission including the 38 patients receiving protocol-specified HSCT with conditioning consisting of individualized targeted doses of busulfan, etoposide, and cyclophosphamide. Three-year event-free survival (EFS) of 56.8% (95%CI, 42.4%-68.8%) and overall survival of 80.2% (95%CI, 67.1%-88.5%) were accomplished. Univariable analysis showed Interfant-HR criteria and flowcytometric minimal residual disease (MRD) ≥0.01% both at end of induction and at end of consolidation (EOC) were significantly associated with poorer EFS. In the multivariable analysis, positive MRD at EOC was solely associated with poor EFS (P<0.001). Rapid pre-transplant MRD clearance and tailored HSCT strategy in the MLL-10 trial resulted in a favorable outcome for infants with HR KMT2A-r ALL. However, considering the high rate of potentially life-threatening toxicities and risk of late effects, its indication should be further restricted or even eliminated in the future by introducing more effective therapeutic modalities with minimal toxicities. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

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.

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