Monosomal Karyotype Predicts Poor Outcome for MDS/sAML Patients with Chromosome 7 Abnormalities After Allogeneic Stem Cell Transplantation for MDS/sAML. A Study of the MDS Subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 293-293 ◽  
Author(s):  
Michel Van Gelder ◽  
Johannes Schetelig ◽  
Liisa Volin ◽  
Johan Maertens ◽  
Gerard Socié ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
High Risk ◽  
Conditioning Regimen ◽  
Working Party ◽  
Chromosome 7 ◽  
Term Survival ◽  
Cytogenetic Abnormalities ◽  
Poor Outcome ◽  
Monosomal Karyotype

Abstract Abstract 293 Background. High-risk MDS/sAML patients have a poor prognosis with conventional therapies. One constant factor predisposing for high risk is the presence of a chromosome 7 abnormality. It is common practice that patients with a chromosome 7 abnormality and other factors that classify them as high-risk are offered allogeneic SCT (alloSCT) as it is believed that this treatment has curative potential. Data on the effect of this approach in these patients are scarce. Methods. The EBMT database was searched for MDS/sAML patients having any chromosome 7 abnormalities and were treated with alloSCT. 278 patients who underwent alloSCT between 1981 and November 2006 were included. Stem cells from related donors were transplanted in 192 patients (177 HLA-identical) while 85 received unrelated grafts. Bone marrow was used as stem cell source in 148 patients while 126 received blood stem cells. Standard conditioning was applied in 222 patients. Sixty-three patients fulfilled the criterion for having complex cytogenetic abnormalities. A monosomal karyotype (MK), defined as at least one monosomy and at least one other chromosomal abnormality (Breems DA et al., JCO 2008;26:4791–7), was present in 63 patients, of whom 23 did not have complex cytogenetic abnormalities. Results. Median follow-up (FU) of patients alive at last FU was 5 years (range, 0–18 years). Estimate 5–year overall (OS), and relapse-free (RFS) survival was 28±5.5% (see figure) and 26±5.5% respectively. The relapse rate at 3, 12 and 60 months was 9±3%, 29±5% and 39±6% respectively. Non-relapse mortality (NRM) at 3, 12 and 60 months was 21±5%, 36±6% and 40±6% respectively. In multivariate models including age, MK, complex karyotype, blasts at alloSCT, donor type, sex match, conditioning regimen, T-cell depletion and year of alloSCT, a MK highly significantly predicted for extremely poor outcome: the adjusted hazard ratios of MK were for OS 2.4 (95% CI, 1.6 to 3.6), for RFS 2.4 (95% CI, 1.7 to 3.9) and for relapse 3.2 (95% CI, 1.8 to 5.7) (p<0.001 for each endpoint). Five-year OS and RFS for patients with a MK were 0% and 0% compared to 37±7% and 34±7% for patients without MK (p<0.001 for both log rank tests) respectively (see figure). Five-year incidences of relapse and NRM of patients with MK were 52±13% and 48±13% compared to 33±7% and 37±7% for patients without MK (gray tests, p=0.002 and p=0.1). Conclusion. This large study of alloSCT for patients with MDS/sAML and any chromosome 7 abnormality shows that long-term survival can be achieved in about 37% of patients without a MK. In contrast, patients with a MK do extremely poor (5-year OS 0%) with standard alloSCT approaches; for these patients new approaches must be explored. Disclosures: Schetelig: Bayer Schering: Research Funding.

Dose-Reduced Conditioning Followed by Allogeneic Stem Cell Transplantation in Patients with Myelofibrosis. Results from a Multicenter Prospective Trial of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 683-683 ◽  
Author(s):  
Nicolaus Kroeger ◽  
Ernst Holler ◽  
Guido Kobbe ◽  
Martin Bornhaeuser ◽  
Rainer Schwerdtfeger ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
Conditioning Regimen ◽  
Working Party ◽  
Unrelated Donor ◽  
Jak2 Mutation ◽  
Cytogenetic Abnormalities ◽  
Excellent Outcome

Abstract The major limitation of allogeneic stem cell transplantatiopn (SCT) in patients (pts) with myelofibrosis is the high treatment related mortality. We performed a prospective multicenter trial of a dose-reduced conditioning regimen, consisting of busulfan (10 mg/kg orally or 8mg/kg i.v), fludarabine (180 mg/m2) and anti-thymocyte globulin (ATG Fresenius: 30–60 mg/kg) followed by allogeneic SCT in pts with myelofibrosis. From 2002 to 2006, 104 pts with a median age of 55 years (range: 32–68) andlow risk with constitutional symptoms (18%) or intermediate risk (n= 58%) and high risk (n=19%) were included. Cytogenetic abnormalities and JAK2 mutation were noted in 22% and 48%, respectively. Bone marrow histology showed advanced fibrosis (MF 2 and 3) in all pts. All but 3 pts received peripheral blood stem cells as graft source either from related (n=33) or unrelated donor (n=71). All but one (1%) pts showed leukocyte and platelet engraftment after a median of 18 and 21 days, respectively. The median duration of leukocyte aplasia was 9 days (range: 3–21). Acute GvHD grade II to IV occurred in 19% and severe aGvHD III/IV in 7%, while chronic GvHD was seen in 32% of the pts. Non-relapse mortality at 1 year was 19% (95% CI: 11–27%) and significantly lower for pts younger than 50 years of age (0% vs 27%, p=0.004) and for pts with low risk vs intermediate/high risk disease (0% vs 27%, p= 0.02). The cumulative incidence of relapse at 3 years was 29% (95%CI: 15–43%). The 3 year overall (OS) and event-free survival (EFS) was 70% (95% CI 60–80%) and 55% (95% CI 42–68%). Significant factors for improved 3 year OS and EFS were age less than 50 years (92% vs 62%, p=0.003 and 79% vs 46%, p= 0,004) and low vs intermediate/high risk (100% vs 62%, p=0.01 and 72% vs 48%, p= 0.02), while no impact on survival was seen for cytogenetic abnormalities, JAK2 mutation status and donor (related vs unrelated). These prospective multicenter study show excellent outcome of an busulafan/fludarabine based reduced conditioning regimen followed by allogeneic SCT in pts with myelofibrosis.

scholarly journals Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant?

2020 ◽  
Vol 9 (8) ◽  
pp. 2354
Author(s):  
Hyunkyung Park ◽  
Ja Min Byun ◽  
Sung-Soo Yoon ◽  
Youngil Koh ◽  
Dong-Yeop Shin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Optimal Timing ◽  
Term Survival ◽  
One Year

Background: Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear. Methods: Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017. Results: The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (<5) before alloSCT had a prolonged RFS and OS. All patients (seven patients) who received a myeloablative conditioning regimen had high-risk features, but two out of seven patients showed long-term survival without lasting sequelae. Nine patients (37.5%) experienced non-relapse mortality (NRM) within one year after alloSCT (the one-year cumulative incidence of NRM was 38.3 ± 10.1%). Conclusion: AlloSCT can still be implemented as effective salvage option in the treatment of relapsed/refractory high-risk MM. The optimal timing of alloSCT remains to be determined.

CD3/CD19 Depleted Grafts for Haploidentical Stem Cell Transplantation in Children: Results of a Pilot Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3121-3121
Author(s):  
Peter J. Lang ◽  
Ingo Mueller ◽  
Johann Greill ◽  
Peter Bader ◽  
Michael Schumm ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Study Group ◽  
Preliminary Results ◽  
Conditioning Regimens ◽  
Active Disease

Abstract Profound depletion of T and B cells is a fundamental prerequisite for haploidentical transplantation. We present our preliminary results with a direct depletion procedure using antiCD3/antiCD19 coated magnetic microbeads and the CliniMACS™ device. Only patients with high risk malignancies (n=25, most of them had active disease or relapsed after previous trp.) or with nonmalignant diseases and high risk of graft failure (n=2) were included. The diagnoses were: AML/MDS/CML (n=13), ALL(n=6), relapsed Neuroblastoma/Ewing-/Rhabdomyosarcoma (n=6), SAA, PNH (n=2); Remission status: NR=8, 2nd transplantation=10, CR/CP1=3, CR2–4=6. The patients received either TBI or Bu based standard conditioning regimens (n=9) or a toxicity reduced protocol (Flud, TT, Mel, OKT3, MMF, n=18). The grafts comprised a median number of 16x106/kg (7–41) stem cells as well as high amounts of NK-cells (137x106 (9–550)) and monocytes/granulocytes (6x108 (0.6–13)) with 49x103/kg (7–200) residual CD3+ cells and <0.01% CD20+ cells. Primary engraftment occurred in 89% of patients (after reconditioning and second stem cell donation:100%). Median time to reach >500 neutrophiles/μl and independence from platelet substitution was 10 and 9 days respectively. Recovery of CD3+ cells was favorable (d90: 320/-l, d180: 600/μl). Acute GvHD grade 0–1 occurred in 74%, 26% had GvHD grade II. Limited chronic GvHD occurred in 4 patients. No transplant related mortality (TRM) and, in particular, no lethal infections were observed. 13/27 patients (49%) were alive with a median follow up of 0.8 years (3 months – 2.1 years). Single cause of death was relapse. Disease status was predictive: 8/9 patients with leukemias and active disease relapsed, whereas only 2/10 patients in CR relapsed. 2/6 patients with solid tumors are alive. Recovery of platelets was faster in patients with CD3/CD19 depleted grafts than in a historical control group of patients (n=53) transplanted with haploidentical positive CD34+ selected standard grafts (23 vs. 9 days, p<0.01). No lethal viral infections occurred in the study group due to the fast T cell recovery, whereas in patients with positive selected grafts a cumulative incidence of 18% was observed. The toxicity-reduced conditioning regimen helped to avoid any other TRM, despite intensive pretreatment (including previous transplantation) of the patients. Conclusions: our preliminary results indicate that CD3/CD19 selected grafts can improve immunoreconstitution and TRM. Engraftment rates similar to that of patients with myeloablative standard conditioning regimens and positive selected stem cells could be achieved, although most patients of the study group received an intensity reduced regimen. However, the outcome was poor in patients with active disease. Thus, further options have to be investigated to increase the potential antileukemic activity of donor derived effector cells.

Poor Outcome after Allogeneic Hematopoietic Stem Cell Transplantation for De Novo AML with Chromosome 7 Abnormalities: A Report for the ALWP of the European Group for Blood and Marrow Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 325-325
Author(s):  
Agnes Buzyn ◽  
Myriam Labopin ◽  
Jurgen Finke ◽  
Tapani Ruutu ◽  
G. Ehninger ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
De Novo ◽  
Conditioning Regimen ◽  
Chromosome 7 ◽  
Partial Deletion ◽  
Hematopoietic Stem ◽  
Monosomy 7 ◽  
Advanced Phase ◽  
De Novo Aml

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many acute myeloid leukemia (AML) patients, especially those with high-risk features. However, for the latter, cure rates remain disappointing due to relapse and transplant related mortality. Since high-risk AML defines a heterogeneous group of patients, the aim of this study was to evaluate specifically the impact of chromosome 7 abnormalities on the outcome of patients transplanted for AML. From 1982 to 2005, 159 de novo AML patients were reported in the EBMT registry with a chromosome 7 abnormality. Median age was 40 years (16–67). FAB subtypes were various: 20 M0, 34 M1, 34 M2, 30 M4, 10 M5, 6 M6, 9 M7, 16 missing. Monosomy 7 was present in 86 patients (54%) either isolated (n=71) or associated to a complex karyotype (n=15), whereas 46% had partial deletion. HSCT was performed in complete remission (CR1) in 85 patients (53%) and for an advanced phase for 69 (43%) defined as either primary refractory (n=49) or progressive (n= 20). The donor was a match sibling (n=88), unrelated donor (MUD) (n=42), or mismatched UD (n=29). The conditioning regimen was myeloablative for 123 patients (77%), containing TBI for 82. Stem cell source was peripheral blood for 97 patients (61%). T cell depletion was performed for 54% of the transplants either in vivo (n=60) or in vitro (n=26). The median follow up of the cohort is 47 months. A GvHD grade II-IV occurred in 47 patients (30%) and III/IV in 28 patients (18%). Among 132 patients alive at day 100, 38% developed chronic GvHD. At time of analysis only 42 patients are alive. The main cause of death is relapse (57%). The univariate analysis shows that the probability of OS at 5 years is 43% for patients transplanted in CR as compared to 11% for advanced phase patients (p<0,0001), and is only 17% for patients with a monosomy 7 compared to 29% for patients with a partial deletion (p=0,007). The survival of patients with AML FAB subtypes M5, 6 or 7 is only 8% compared to 24% for other subtypes (p=0,03). The year of transplant, T cell depletion, type of donor, conditioning regimen, cell source, and patients age have no influence on survival. In the multivariate analysis, CR at transplant (p= 0,005) and partial deletion of chromosome 7 (p=0,02) are the only two factors associated with a better 5 years OS. In conclusion, patients with abnormalities of the chromosome 7 and specially those with monosomy 7 represent a very high risk group of AML patients after HSCT, mostly because of the relapse risk, suggesting a very poor graft-versus-leukemia (GvL) effect in this disease which does not seem to be improved by the use of an UD. Thus, new approaches attempting to decrease the relapse rate of de novo AML with chromosome 7 abnormalities after HSCT are urgently needed.

Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-SCT) with Pre-Transplant Immunosuppression (PTIS) and Post-Transplant Cyclophosphamide (Post-Cy) in Severe Thalassemia: Safe Approach and Excellent Disease Control

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2571-2571
Author(s):  
Suradej Hongeng ◽  
Samart Pakakasama ◽  
Usanarat Anurathapan ◽  
Borje Andersson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Risk Class ◽  
Donor Chimerism

Abstract Background Currently, the thalassemia free survival rate after hematopoietic stem cell transplant (HSCT) is about 80-90% with either matched sibling or unrelated donor. However, the probability to find a suitable door is only 25-50%. Since most of these patients (pts) could not find the potential donor, we would like to investigate the haploidentical donor HSCT (Hapo-SCT) in thalassemia. Patients and Methods Between Jan 2013 and August 2014, 12 thalassemia patients (pts) underwent haplo-HSCT. Six subjects were male and 6 were female. The median age was 16 yrs (range; 2-22). Nine of 12 received stem cells from mother and 3 from father. Ten of 12 were high risk class 3. These high risk class 3 pts received hydroxyurea 20 mg/kg/d for at least 3 months prior to HSCT. All pts received 2 courses of pre-transplant immunosuppression (PTIS) consisting of fludarabine (Flu) 40 mg/m2/d together with dexamethasone (dex) 25 mg/m2/d for 5 days. After 2 courses of PTIS, all pts received a reduced-toxicity conditioning regimen consisting of thymoglobulin 1.5 mg/kg/d (d-11 to d-9), Flu 35 mg/m2/d i.v. (-7 to -2) each dose immediately followed by busulfan (Bu) 130 mg/m2once daily i.v. (d-7 to d -4) for pts > 10 years and 0.95-1.2 mg/kg every 6 hr (d-7 to d-4) for pts < 10 yrs. GVHD prophylaxis consisted of cyclophosphamide (Cy) 50 mg/kg/d (d +3 to d+4). Tacrolimus was given for 6 months to 1 yr started together with mycophenolate mofetil on d+5, the latter was quickly tapered after 2 months. T-cell repleted peripheral blood stem cells (PBSC) were given to all pts, targeting a CD34+ dose of 7-10 x 106cells/kg. Results Eleven of 12 were engrafted with full donor chimerism (100%) while one pt suffered graft failure. However, this pt received second transplant on day +30 with minimal conditioning regimen and additional PBSC after which she achieved full donor chimerism. The median time to neutrophil engraftment was 18 days (range; 14 -22). Four pts had acute GVHD gr I, 2 grade II and 1 gr III. Only one had limited chronic GVHD. At this time, all 12 pts survive thalassemia-free and have sustained full donor chimerism (100%). Thalassemia free survial and overall survival rates are 100%. The median follow up time is 12 months (range 4-20). Conclusion Haploidentical HSCT for high risk thalassemia pts with our novel approach is safe and should be considered as modality to secure thalassemia-free survival with a low risk for graft rejection and treatment-related mortality. In view of our results, we suggest that all thalassemia pts even those with high risk class 3 features should be offred the chance for cure with HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcome of Severe Aplastic Anemia Post Allogenic Stem Cell Transplant with Mycophenolate and Calcineurin Inhibitor for Graft Versus Host Disease Prophylaxis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4879-4879
Author(s):  
Omar Albanyan ◽  
Hyejeong Jang ◽  
Seongho Kim ◽  
Andrew Kin ◽  
Asif Alavi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Matched Donor

Abstract Introduction: Severe aplastic anemia (SAA) is a rare hematopoietic stem cell disorder characterized by hypocellular marrow and pancytopenia. Multiple factors play an important role in treatment approach include age, comorbidities, degree of pancytopenia and availability of stem cell donor to either immunosuppression irrespective (IST) or allogenic hematopoietic stem cell transplant (alloSCT). The use of nonmyeloablative conditioning regimen has improved the outcomes, however the choice for post-transplant GVHD prophylaxis remain a topic of debate. The use of mycophenolate mofetil (MMF) has been used as an alternative for methotrexate (MTX) as has shown to be associated with lower incidence of mucositis and shorter time to engraftment. Methods: We retrospectively evaluated consecutive adult patients with SAA who underwent alloSCT at Karmanoc Cancer Institute. All patients received fludarabine, cyclophosphamide and antithymocyte globulin for conditioning regimen with calcineurin inhibitors (CNI) and MMF for GVHD prophylaxis. MMF was started at day -3 at 15 mg/kg three times daily and stopped at day +30 in the absence of active GVHD. The primary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and overall survival (OS). Secondary objectives were to evaluate time to engraftment, days of hospitalization and incidence of mucositis. Results: From January 2005 and May 2019, 33 patients with SAA underwent alloSCT. Patient characteristics are detailed in Table 1. Median age was 36 years (range, 18-71). Twenty-seven patients received bone marrow stem cells (82%) and six patients received peripheral blood stem cells (18%). Thirty patients (91%) received 8/8 HLA matched donor and three patients (9%) received 7/8 HLA matched donor. Sixteen patients (48%) received stem cells from sibling donor and 17 patients (52%) received stem cells from unrelated donor. Thirteen patients (39%) had received IST prior to alloSCT, and 20 patients (61%) received upfront alloSCT. For GVHD prophylaxis all patients received MMF and CNI (tacrolimus=32, and cyclosporine=1). Median time from diagnosis to transplant was 15.8 months for patients who received IST prior to alloSCT and 2 months for patients who received upfront alloSCT. Median time to platelet engraftment was 13.5 days and neutrophil engraftment was 12 days, while one patient experienced graft failure. The median number of days for hospital stay were 25 days. Four patients (11%) developed grade I-II mucositis, no grade III-IV mucositis was observed in the first 30 days and 6 patients had CMV reactivation. The 100-day cumulative incidence rate of grade II-IV aGVHD was 21.2% (95% CI, 9.2 - 36.5), grade III-IV aGVHD was 9.1% (2.3-21.9) and 1-year CIR of cGVHD was 21.2% (95% CI, 9.2-36.5). Comparing patients who received IST prior to alloSCT versus upfront alloSCT, the 100-day CIR of grade II-IV aGVHD was 30.8% (95% CI, 8.2 - 56.5) and 15% (95% CI, 3.6 - 34.0), respectively, (Gray p=0.26) and the 3-year CIR of cGVHD was 39.6% (95% CI, 13.1 - 65.5) and 27.8% (95% CI, 9.2 - 50.3), respectively, (Gray p=0.37). Comparing patients who received alloSCT from related versus unrelated donor, 100-day CIR of II-IV aGVHD was 12.5% (95% CI, 1.9 - 33.6) and 29.4% (95% CI, 10.2 - 51.9), respectively, (Gray p=0.26), and the 3-year CIR of cGVHD was 34.2% (95% CI, 11.4 - 58.9) and 29.4% (95% CI, 10.1 - 52.0), respectively (Gray p=0.90). Median follow up of surviving patient was 5 years (95% CI, 3.1-6.8). Three-year OS was 87% (95% CI, 75.7- 99.9) and median OS was not reached. Six patients died by the time of the analysis, one patient died from graft failure (86 days after transplant from 8/8 HLA MUD), two patients died due infectious complications (808 days and 1637 days after transplant), three patients died due to multiorgan failure (215, 297 and 1097 days after transplant). Conclusion: Our data with use of CNI and MMF for GVHD prophylaxis for SAA following alloSCT with nonmyeloablative conditioning regimen showed that the rate of mucositis was low, engraftment time was rapid, and hospitalization was short, while OS, rates of acute and chronic GVDH were comparable to previously published rates with CNI and MTX-based GVHD prophylaxis. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

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