Influence of Lower Dose Antithymocyteglobulin As Conditioning Regimen on Viral Infection after Haploidentical Allogeneic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 825-825 ◽  
Author(s):  
Ren Lin ◽  
Yu Wang ◽  
Fen Huang ◽  
Zhiping Fan ◽  
Shen Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Viral Infection ◽  
Cell Transplantation ◽  
Natural Science ◽  
Research Funding ◽  
Viral Infections ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Background: Antithymocyteglobulin (ATG), used as conditioning regimen, can reduce graft-versus-host disease (GVHD) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Notwithstanding, immunosuppressive effect of ATG may increase the risk of viral infections after HSCT. To evaluate the effect of different doses of ATG on post-transplant viral infection, we conducted a multicenter prospective study to compare EBV and CMV infection in haplo-HSCT recipients receiving 7.5 mg/kg or 10 mg/kg ATG. Methods Between May 2013 and November 2015, 350 consecutive patients with hematological malignancies undergoing haplo-HSCT were randomized in 5 hospitals. One hundred and seventy-two patients received ATG with a total dosage of 7.5 mg/kg and 175 received 10 mg/kg ATG. Three patients did not received allocated intervention and transplantation due to leukemia relapse before transplant or toxicity of conditioning regimens. Results The cumulative incidence of EBV viremia on day 180 was 23.3±3.2% in 7.5 mg/kg ATG arm which was lower than that in 10 mg/kg arm (34.6±3.7%, P=0.037). CMV viremia were comparable in the two arms (7.5 mg/kg arm: 79.0±3.1% vs. 10 mg/kg arm: 76.9±3.2%, P=0.950). The incidences of CMV diseases were 0.6±0.6% and 2.4±1.2% in 7.5 mg/kg and 10 mg/kg arms, respectively (P=0.093). No difference in the incidence of post-transplant lymphoproliferative disorder (PTLD) was found between the two arms (2.4±1.2% in 7.5 mg/kg arm vs. 5.4±1.8% in 10 mg/kg arm, P=0.150). Besides, acute GVHD grade II to IV within 100 days occurred in 55 recipients with the incidence of 31.4% in 7.5mg/kg ATG arms and 45 recipients in 10 mg/kg arms with the incidence of 26.2% (P=0.279). The incidences of aGVHD grade III to IV were similar in the two arms (8.0% in 7.5 mg/kg arm: vs. 4.7% in 10 mg/kg arm, P=0.196). The 2-years overall survival were 69.5±4.7% and 69.4±3.9% for 7.5 mg/kg and 10 mg/kg group (P=0.540). Conclusion Compared with 10 mg/kg of ATG, the application of 7.5 mg/kg might reduce the risk of EBV infection after haplo-HSCT and not increase aGVHD. Disclosures Lin: National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding; National Natural Science Foundation of China 81400141: Research Funding.

scholarly journals The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4858-4858
Author(s):  
Federica SORA ◽  
Patrizia Chiusolo ◽  
Sabrina Giammarco ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Total Dose ◽  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age >60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

scholarly journals The association of conditioning regimen with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

2020 ◽  
Author(s):  
Masoud Mardani ◽  
Sara Abolghasemi ◽  
Shiva Shabani ◽  
Farzaneh Tavakoli ◽  
Anahita Saeedi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Background and Objectives: Infections is yet one of the life-threatening complications of the hematopoietic stem cell transplantation (HSCT). The myeloablative and immunosuppressive conditioning regimens, which are administered before HSCT, dampen the defense capacity of the recipients’ immune systems. In this condition, opportunistic infections, especially viral infections such as cytomegalovirus (CMV) can be reactivated and cause morbidity and mortality in HSCT patients. Here, we aimed to find out any possible relationship between types of conditioning regimen and CMV reactivation in allo- geneic HSCT patients. Materials and Methods: We retrospectively analyzed the data of 145 CMV-seropositive cases out of total 201 allo-HSCT patients, including age, gender, underlying disease, conditioning regimen, prophylaxis regimen and occurrence of acute graft-versus-host disease (aGVHD) to evaluate their roles in CMV reactivation. Results: Our result showed that conditioning regimen containing Busulfan and Fludarabine (P=0.003) or Cyclophospha- mide (P=0.02) significantly decrease the early CMV reactivation. Patients who developed aGVHD (P=0.003) and those who received anti-thymocyte globulin (ATG) as prophylaxis regimen (P=0.002), had 1.84 and 2.63 times higher risks of CMV reactivation, respectively. Conclusion: Our findings suggest the conditioning regimen, aGVHD and ATG as influencing factors for early CMV reacti- vation post-HSCT which should be considered in the future studies.

Role of Allogeneic Hematopoietic Stem Cell Transplantation for None Remission / Advanced Acute Myeloid Leukemia with Flt3-Itd Mutations: Outcomes of 15 Newly Diagnosed Patients from a Single Institution

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5936-5936
Author(s):  
Zhiping Fan ◽  
Qifa Liu ◽  
Jing Sun ◽  
Yu Zhang ◽  
Fen Huang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Natural Science ◽  
Research Funding ◽  
Guangdong Province ◽  
Hematopoietic Stem ◽  
Guangzhou City ◽  
Disease Free

Abstract Backgrouds : Acute myelogenous leukemia (AML) patients with FLT3-ITD mutations have an inferior survival compared to AML patients with wild-type (WT) FLT3, primarily because of an increased relapse rate. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a postremission therapy that is effective at reducing the risk of relapse for many cases of poor-risk AML. Whether or not allo-HSCT can improve outcomes for patients with none remission/advanced FLT3-ITD mutation AML is not known. Objective : To compare the effect of allo-HSCT between none remission/advanced FLT3-ITD positive AML and other none remission/advanced AML excluding FLT3-ITD mutations. Patients and methods : We analyzed 49 patients who underwent allo-HSCT with a diagnosis of none remission/advanced AML on FLT3-ITD mutations between February 2012 and Apiril 2014. Fifteen patients were FLT3-ITD positive and 24 were FLT3-ITD negative. Transplantations were performed in none remission/advanced status after myeloablative conditioning or intensified conditoning. Results : Patient’s characteristics were similar in the two groups, including leukocyte count at diagnosis, interval from CR to transplant, disease status, donor type, stem cell resource, prepare regimens, and graft versus host disease (GVHD) prophylactic protocols. All patients achieved hematopoietic engraftment. The time to neutrophil and platelet engraftment was similar between the two groups. The incidences of acute GVHD and chronic GVHD were comparable between the two groups. At 2 year after transplantation, cumulative relapse incidence (33.3% ± 14.9% v 18.5% ± 7.7%; P =0.335) and disease-free survival (DFS) were not different (51.9% ± 15% v 61.4% ± 8.9%; P =0.749) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. The overall survival between the two groups was also similar (57.0% ± 14.8% v 62.1% ± 9.3%; P =0.834). Conclusions : FLT3-ITD didn’t affect the outcome of HSCT for none remission/advanced patients in the same direction it does after chemotherapy; and more than half of the patients harboring this mutation who received transplants were alive and disease free at 2 years. Disclosures Liu: National Natural Science Foundation of China (81270647, 81300445, 81200388): Research Funding; National High Technology Research and Development Program of China (863 Program) (2011AA020105): Research Funding; National Public Health Grand Research Foundation (201202017): Research Funding; Natural Science Foundation of Guangdong Province (S2012010009299): Research Funding; the project of health collaborative innovation of Guangzhou city (201400000003-4, 201400000003-1): Research Funding; the Technology Plan of Guangdong Province of China (2012B031800403): Research Funding; the project of the Zhujiang Science & Technology Star of Guangzhou city (2013027): Research Funding.

scholarly journals IMMUNITY TO INFECTIONS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION

2016 ◽  
Vol 8 ◽  
pp. 2016057 ◽  
Author(s):  
Franco Aversa ◽  
Lucia Prezioso ◽  
Ilenia Manfra ◽  
Federica Galaverna ◽  
Angelica Spolzino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Post Transplant

The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs), others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC)   showed promise in decreasing early transplant-related mortality (TRM), and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

scholarly journals Hematopoietic Recovery and Transfusion Needs after Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Adult Patients with Hematologic Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2109-2109
Author(s):  
Razan Mohty ◽  
Florent Malard ◽  
Annalisa Ruggeri ◽  
Eolia Brissot ◽  
Remy Dulery ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Donor Age ◽  
Platelet Recovery ◽  
Post Transplant ◽  
Hematopoietic Recovery ◽  
Haploidentical Stem Cell Transplantation

Abstract Introduction: Haploidentical stem cell transplantation (Haplo-SCT) using post-transplant cyclophosphamide is widely used for the treatment of patients with hematologic malignancies especially in patients who lack related or unrelated donors. Several factors were shown to affect hematopoietic recovery after allogeneic hematopoietic stem cell transplantation, including age at transplant, initial diagnosis, stem-cell source, CD34 count in the graft, conditioning regimen intensity, infections, etc. The aim of this study was to evaluate immune reconstitution, neutrophils and platelets recovery, transfusion needs and main transplant outcomes after Haplo-SCT and to identify factors correlated with improved or worsened recovery. Methods: This study included 72 consecutive patients who underwent haploidentical stem cell transplantation between December 2012 and March 2018, in a single center. Graft was either bone marrow (n=21) or peripheral blood stem cells (n=51). Patients were given PT-Cy (50mg/kg/d) for one (n=20) or two days (n=52), cyclosporine, mycophenolate mofetil and ATG for GvHD prophylaxis. Conditioning regimen was reduced toxicity one (RIC) in 69% (n=50) of patients, and a myeloablative one (MAC) in 31% (n=22) of cases . Main transplant outcomes, neutrophil and platelets recovery, and needs for transfusion were evaluated at day +30, day +60 and day +90 after Haplo-SCT. Results: The median CD34+ cells infused was 10.62 x106/kg (range, 1.02-15.06). The median time to neutrophil recovery (>500/µL) was 16 days post-transplant (range, 5-29). The median time to neutrophil count >1000/µL was 17 days post-transplant (range, 5-32). Platelets recovery (>20.000/µL) was observed at a median of 13 days post-transplant (range, 10-193). Platelets recovery (>50.000/µL) was documented at a median of 60 days post-transplant (range, 10-193). Forty-five (63%) and 49 (68%) patients had a platelets count >50.000/µL at days +30 and +60 post-transplant respectively. At day +90 post-transplant, 61 patients were assessable with 56 (92%) of them having a platelets count >50.000/µL. In this series, 61 patients (85%) needed platelets transfusion with a median number of 13 units (range, 2-60), transfused for a median of 26 days (range, 5-198) post-transplant. Similarly, 59 patients (82%) needed RBCs transfusion and received a median of 6 RBCs packs (range, 1-60) for a median duration of 31 days (range, 5-147) post-transplant. 23 patients (32%) had anemia and/or thrombocytopenia requiring the administration of growth factors, either erythropoietin in 14 patients (19%) (Epoetin, n=8 or Darbepoetin, n=6) and/or Thrombopoietin in 15 patients (20%) (Romiplostim, n=13 or Eltrombopag, n=2). In all, 6 patients received unmanipulated CD34+ donor stem cell ("boost" procedure), 5 of them for poor graft function and 1 patient as a consolidation after immunosuppressive therapy for relapse after Haplo-SCT. Such boost proved to be successful in 4 patients while 2patients had an incomplete response with persistent anemia and/or thrombocytopenia. In the multivariable analysis, donor age (>40 years) and CMV reactivation within the first 3 months were shown to meaningfully affect day +90 platelets recovery >100 x109/L (HR 4.86, 95%CI 1.08-21.80, p=0.04 and HR 5.15, 95% CI, 1.22-21.7, p=0.03). Number of CD34, conditioning regimen, stem cell source, donor age and disease status at transplant have no impact on platelet recovery at day +90. Conclusion: In conclusion, our data show that Haplo-SCT is associated with a fast hematopoietic recovery with an acceptable rate of transfusions. While the adverse impact of CMV reactivation on platelet recovery was expected, the relation between donor age (>40 years) and platelets recovery is new. This finding should guide in selection of potential donors for Haplo-SCT. Disclosures Mohty: Celgene: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Molmed: Consultancy; Bristol Myers: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Allogeneic hematopoietic stem cell transplantation for cutaneous T-cell lymphoma (CTCL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7540-7540
Author(s):  
C. Hosing ◽  
M. Donato ◽  
I. F. Khouri ◽  
D. T. Chu ◽  
D. L. Bethancourt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Treatment Regimens

7540 Background: Patients (pts.) with advanced CTCL have a poor prognosis. There has been limited experience with the use of allogeneic hematopoietic stem cell transplantation (HSCT) in these pts. We report the results of 11 pts. with advanced CTCL/Sezary syndrome who underwent allogeneic HSCT at our institution. Patients and Methods: All pts. signed informed consent. Median age at the time of HSCT was 50.5 years (range, 22–63). There were 8 F/3M. All were diagnosed with stage IV disease. The median number of prior treatment regimens was 5.5 (range, 3–11). Treatment regimens included PUVA, TSEB, ECP, topical therapy, retinoids, bexarotene, denileukin diftitox, and multiagent chemotherapy. Seven pts. had a PR to treatment administered prior to transplantation, 2 pts. were in CRu and 2 pts. had SD. The conditioning regimen was fludarabine (125 mg/m2), melphalan 140 mg/m2 in 8 pts., fludarabine (125 mg/m2), cyclophosphamide (3 g/m2) ± rituximab in 2 pts., and fludarabine (120 mg/m2), busulfan (11.2 mg/m2) in 1 pt. Patients who received unrelated or mismatched related stem cells also received ATG. GVHD prophylaxis was with tacrolimus/methotrexate in all patients. Results: Ten of 11 pts. engrafted with a median time to ANC >500 mm3 of 12 days (range, 8–14). One pt. died at 17 days post transplant without engraftment due to sepsis. One pt. developed autologous reconstitution and underwent a 2nd allogeneic HSCT procedure and remains in CR at 3 years post transplant. Of the remaining 9 pts., 7 achieved full donor chimerism and 2 pts. were mixed chimera. At the time of this report 4 of 11 pts. have died. Cause of death was sepsis in 2, fungal pneumonia in 1, and PD in 1 pt. Three pts. relapsed post transplant, all 3 were induced back in to a CR by tapering of immunosuppression (2) or DLI (1). Overall 7 pts. continue to be alive and remission with a median follow up of 2.9 years (range, 3 months to 4.4 years). Four of 7 pts. have cGVHD requiring treatment (Table). Conclusions: Allogeneic HSCT is an effective therapy for refractory CTCL/SS and merits further evaluation. [Table: see text] No significant financial relationships to disclose.

scholarly journals Multiplex PCR for Virus Infections after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5845-5845
Author(s):  
Natsuko Inazawa ◽  
Tsukasa Hori ◽  
Masaki Yamamoto ◽  
Keita Igarashi ◽  
Hiroyuki Tsutsumi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Viral Infection ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Viral Infections ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background: Viral infections following hematopoietic stem cell transplantation (HSCT) are thought to occur due to breakdown of both cell-mediated and humoral immunity. We used a multiplex polymerase chain reaction (PCR) method to detect 13 different viral infections from before to six weeks after transplantation. Methods: One hundred and five patients who underwent allogeneic HSCT between September 2010 and December 2012 were included. Weekly blood samples were collected from prior to transplantation to 42 days after transplantation. We used whole blood for comprehensive analysis for the following 13 viruses; herpes simplex virus 1 (HSV-1); HSV-2 varicella-zoster virus (VZV); Epstein-Barr virus (EBV); cytomegalovirus (CMV); human herpesvirus 6 (HHV-6); HHV-7; HHV-8; Adeno virus (ADV); BK virus (BKV); JC virus (JCV); parvovirus; and hepatitis B virus (HBV). Results: Viruses were detected in 75 (71.4%) patients. Before transplantation, four types of viruses were detected in 12 patients. The detection rate gradually increased following transplantation; the number of patients having at least one type of virus peaked at 45 (45.5%) on post-transplant day 21. The most frequently detected virus during the HSCT courses was HHV6 (n=63; 60.0%), followed by EBV and CMV (n=11 each; 10.5%). No other viruses were detected. Viral infections were significantly more common among patients undergoing CBT, those with HLA mismatched HSCT, those treated with either steroids, and those with GVHD. EBV infection tended to be more common in children than in adults. No sex- or pretreatment-related differences were observed in the viral infection rate. Conclusion: These results suggest that in the presence of these factors, we should pay attention to the increased risk of viral infection. Disclosures No relevant conflicts of interest to declare.

scholarly journals Contemporary Conditioning Regimen before Allogeneic Stem Cell Transplantation for Children with Non-Malignant Diseases

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3398-3398
Author(s):  
Christina Peters ◽  
Mary Slatter ◽  
Paul Veys ◽  
Franco Locatelli ◽  
Adriana Balduzzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Bone Marrow Failure ◽  
Conditioning Regimen ◽  
Common Disease ◽  
Malignant Diseases ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Non-malignant diseases (NMD) include a wide spectrum of either congenital or acquired disorders occurring in early and later childhood. The primary goal of conditioning in NMD is either the replacement of missing cells as in severe aplastic anaemia (SAA) or severe combined immunodeficiencies (SCID) or the exchange of a deficient blood cell compartment as in hemoglobinopathies, hemophagocytic syndromes or metabolic disorders. The right choice of a conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT) is crucial for the outcome of patients with NMD, many of whom are often critically ill due to infections, organ dysfunctions, vascular complications or metabolic problems. As a consequence of a highly activated immune-system and no pre-treatment with chemotherapy, graft rejection is a known severe complication in these patients. To get up-to-date information on the most commonly used conditioning regimen for children with NMD, we performed an EBMT- registry-based analysis: 2187 patients from 39 countries with a congenital or acquired NMD below the age of 18 years who underwent first allogeneic HSCT between January 2010 and December 2014 registered in the EBMT database were included. 51% of children were transplanted before 4 years of age, 489 patients were less than 12 months old, and 61.5% were male. Majority of patients (32,2%) underwent HSCT for hemoglobinopathies (463 thalassemia major, 127 sickle cell disease), the second most common disease type was SCID with 17.4%, followed by other primary immunodeficiencies, chronic granulomatous disease and bone marrow failure syndromes (excluding Fanconi anaemia): 13.2%, 11% and 10.4%, respectively. The given conditioning regimen was under discretion of the treating physician. The most common conditioning regimen consisted of a combination of busulfan (bu)/fludarabine (flu) in 1063 patients, of treosulfan (treo)/flu in 422 patients; 473 patients received a combination of treo/flu/thiotepa (tt) and 229 patients received bu/flu/tt. The median total dose of the respective conditioning drugs was comparable (treo: 41 g/m2 or 42g/m2; bu: 160 mg/m2; tt: 201 and 205 mg/m2). In univariate analysis, overall survival (OS) was significantly different between the conditioning groups (p = 0.0032): 2y-OS 87.7% [84.3%-91.2%] for treo/flu/tt vs. 82.4% [78.5%-86.5%], 81.8% [77.8%-86.0%] for treo/flu, 80.8% [78.1%-83.5%] and 78.2% [75.2%-81.3%] for bu/flu and 81.3% [75.9%-87.0%] and 80.4% [74.9%-86.4%] for bu/flu/tt, respectively. Transplant-related mortality (TRM) was significantly different between the conditioning groups (p = 0.0015): day-100 TRM was lowest after treo/flu/tt: 4.8% [2.8%-6.7%] compared to 9.2% [6.3%-12.0%] after treo/flu, 7.9% [6.2%-9.5%] after bu/flu and 9.9% [5.9%-13.8%] after bu/flu/tt. TRM at 1 year post-transplant: 8.3% [5.5%-11.0%] for treo/flu/tt, 16.2% [12.2%-20.0%] after treo/flu, 16.9% [14.2%-19.4%] after bu/flu and 14.9% [9.7%-19.8%] after blu/flu/tt, respectively. In multivariate analysis, the HR was adjusted on age groups at HSCT, underlying disease, year of HSCT, stem cell source and donor types. 1-y OS was significantly better after treo/flu/tt (89.5 [86.5 - 92.6], CI 95%, p 0.0032) than with treo/flu, bu/flu or bu/flu, respectively. Day 100- and 1-year TRM was lower after treo/flu/tt compared to the other three conditioning combinations. A pairwise testing of the different treatment groups revealed no statistical significant difference in OS, TRM, disease-free survival (DFS) for bu/flu vs. treo/flu, bu/flu vs. bu/flu/tt and bu/flu/tt vs. treo/flu; a significant better OS, DFS and less TRM for treo/flu/tt vs. bu/flu, treo/flu/tt vs. treo/flu and a better DFS for treo/flu/tt vs. bu/flu/tt with a trend for better OS and less TRM for treo/flu/tt vs. bu/flu/tt. No statistically significant differences were found among the 4 conditioning regimens for acute or chronic GVHD. Conclusion: For children with NMD, a variety of conditioning regimen are in use to facilitate engraftment, prevent rejection, and enable sufficient cell function. Beside treo and bu, flu and tt are established drugs to eradicate lymphocytes. In this analysis, the combination of treo/flu/tt shows promising outcome results and should be further evaluated in diseases specific prospective trials. Disclosures Peters: Pfizer: Consultancy; Amgen: Consultancy; Jazz: Speakers Bureau; Novartis: Consultancy; Medac: Consultancy. Slatter:Medac: Other: Travel grants. Bader:Medac: Consultancy, Research Funding; Riemser: Research Funding; Neovii Biotech: Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients with Acute Myeloid Leukemia: Analysis of the Francophone Society for Stem Cell Transplantation and Cell Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3447-3447
Author(s):  
Regis Peffault De Latour ◽  
Matthieu Resche-Rigon ◽  
Didier Blaise ◽  
Johan Maertens ◽  
Patrice Ceballos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Sibling Donor

Abstract Background: Nowadays acute myeloid leukemia (AML) patients above the age of 60 years are often candidates for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT). However, little is known about the outcomes of HSCT in this particular population, due to the low number of HSCT with robust follow-up, the heterogeneity between centers, as well as reports usually mixing AML and other diseases such as myelodysplastic syndrome. We used the database of the Francophone society for stem cell transplantation and cellular therapy to address this question in a large cohort of patients in a recent time period. Patients and methods: 1167 consecutive patients aged ≥60 years with AML in complete remission (CR), transplanted between January 1st 2006 and January 1st 2016, reported to ProMISe (Project Manager Internet Server), an internet-based system shared by 36 Francophone transplantation centers, were reviewed. Classical post-HSCT endpoints were studied such as engraftment, acute and chronic graft-versus-host disease (GvHD), non-relapse mortality (NRM), relapse rate, leukemia free survival (LFS) as well as overall survival (OS). Cytogenetic risk was assessed according to the European Leukemia Network 2017 for patients in first complete remission. Data were analyzed using proportional hazards models and proportional sub-distribution hazards models in presence of competing risks. Results: Patients' Characteristics are detailed in Table 1. The median age at HSCT was 62.9 years (Interquartile range -IQR 61.9-66.1). Patients aged ≥60 years but less of 65 represented 63.8% of the population with 68.2% of patients transplanted in the recent period (2011-2016). Most patient had de novo AML (91.6%), in first CR (76.9%) with intermediate risk (83.8%) according to ELN-2017 classification. A matched unrelated donor (MUD) was used in 45 % of transplants and the majority of patients received peripheral blood stem cells (83.7%). Half of the patients received fludarabine and 2 days busulfan as conditioning regimen. The majority of patients (70.9%) received anti-thymocyte globuline (ATG). Engraftment occurred in 1089 patients (93.3%; 95%CI, 91.9-94.8). Day 100 cumulative incidence of grade II-IV acute GVHD was 24.6% (15.7% grade II; 5.8% grade III; 3% grade IV). At last follow up, 378 patients had developed chronic GVHD (severe in 37.2% of them; 95%CI, 34.0-40.3). With a median follow-up of 3.5 years (95%CI, 3.1-3.7 years), overall survival (OS) and LFS probabilities at 3 years were 50.7% (95%CI, 47.7-54.0) and 44.8% (95%CI, 41.8-48.1), respectively. In multivariable analysis, the only factor associated with worse OS was the use of a mismatched unrelated donor compare to MUD [Hazard Ratio (HR): 1.35 (95% CI, 1.01 to 1.80), p=0.04]. At 3 years, relapse incidence was 34.4% (95% CI, 31.5-37.4). The use of a sibling donor compared to MUD [Sub-distribution Hazard Ratio (SHR): : 1.49 (95% CI, 1.19 to 1.87), p<0.001], poor risk AML in CR1 according to ELN classification [SHR: 1.49 (95% CI, 1.10 to 2.02), p=0.01], as well as the use of ATG in the conditioning regimen [SHR: 1.57 (95% CI, 1.21 to 2.05), p<0.001] were associated with a higher risk of relapse. During the study, 534 patients died (main causes of death was relapse, 53%); leading to a CI of NRM of 20.7% at 3 years (95%CI, 18.2-23.2). A karnofsky score above 90% [SHR: 0.74 (95% CI, 0.56 to 0.98), p=0.04] and the use of a sibling donor compare to MUD [SHR : 0.43(95% CI, 0.30 to 0.63), p<0.001] were associated with reduced NRM. Conclusion: With more than 3 years follow-up, which is long enough for our results to be considered to be robust, the use of a mismatched unrelated donor was the only factor associated with worse overall survival in this population of AML patients aged of 60 years or more. Relapse appeared as the first cause of death, independently related to AML ELN poor risk classification, but also to the use of a sibling donor and of ATG in the conditioning regimen. This study highlights the major role of alloreactivity in this particular population, where modulation of T-cell alloreactivity as well as donor choice should be urgently addressed in well-designed prospective trials. Disclosures Peffault De Latour: Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

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