scholarly journals Outcome of Patients Receiving Extracorporeal Photopheresis for Steroid Resistant Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5720-5720
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Alexandre Deloire ◽  
Daniela Revesz ◽  
Youcef Chelgoum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Extracorporeal Photopheresis ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Methyl Prednisolone ◽  
Gvhd Prophylaxis ◽  
Grade Iii

Abstract Introduction: Graft-versus-host disease (GVHD), and complications of its treatment are the major causes of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). With the use of standard GVHD prophylaxis with classical administration of Anti-thymocyte globulin (ATG), calcineurin inhibitors (CNIs) and methotrexate, the incidence of acute and chronic forms of GVHD remains not negligible. Extracorporeal photopheresis (ECP) has shown very promising results as curative strategy for GVHD but also when used prophylactically. The primary objective of this observational study was to perform an exhaustive description concerning patients receiving ECP after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes. Patients and methods: We included 82 patients who underwent allo-HCT between years 2001 and 2016, 50 (61%) were males, median age at allo-HCT was 52 years (20-67). Major diagnoses were acute leukemias (45%), myelodysplastic syndromes (17%) and multiple myeloma (11%). Before transplantation, 43 (52%) patients were in complete remission or in chronic phase. Donors were identical siblings in 51% of patients, matched unrelated in 24%, mismatched unrelated in 24% and haploidentical in 1%. Hematopoietic Stem Cell source was peripheral blood in 65%, bone marrow in 27% and cord blood in 8%. Conditioning regimens were non myeloablative in 63% cases and myeloablative in 37%. ATG was used during conditioning in 63% of patients. GVHD prophylaxis consisted on cyclosporine A (CsA) alone in 21% of patients, CsA + mycophenolate mofetil in 27%, CsA + methotrexate in 26%, the rest received other combinations. In acute GVHD, first treatment consisted in methyl-prednisolone 2mg/Kg/day in combination with CNIs; and in chronic GVHD, it was methyl-prednisolone 0.5 - 1 mg/Kg/day + CNIs. ECP was performed using peripheral venous access. ECP was initiated after transplantation either for acute GVHD [N=28 (34%), 9 grade II, 3 grade III and 16 grade IV] affecting skin alone (N=5), gut alone (N=14), gut + liver (N=8); or for chronic GVHD [N=54 (66%), 19 (35%) limited and 35 (65%) extensive]. A total of 3300 ECP sessions were performed, majority were twice a week; the median number of sessions/patient was 21 (min: 2, max: 131) for a median duration of 4.2 months (range: 0.5-73). ECP response evaluation was assessed after 4 weeks of treatment, patients were considered responding to ECP if more than 50% resolution of clinical GVHD manifestation of the organ involved was registered. Results: Among the 28 patients treated for acute GHVD, one was not evaluable because of disease progression and early death, 11/27 (41%) were responders to ECP and 16/27 (59%) were not responders and died later from GVHD associated to other complications. Among the 54 patients with chronic GVHD, 32/54 (59%) were responders. Of note, in both forms of acute and chronic GVHD, responding patients had more skin forms whereas non-responding patients has more organ-involved forms especially liver and gut. After a median follow-up of 26 months, 32 (39%) patients are alive and 50 (61%) died, 43 from TRM causes (17 in the aGVHD group and 26 in the cGVHD group). Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 31% [95%CI: 14-56], those with chronic GVHD had a median OS of 36 months with a survival probability at 2 years of 55% [95%CI: 40-78]. Patients with chronic GVHD had better PFS probability at 2 years with 55% (95% CI: 43-70) versus 27% (95% CI: 14-51) for those with acute GVHD, p=0.007. In stepwise multivariate analysis, acute GVHD grade III-IV, significantly impacted on OS (HR=7.77, 95%CI: 1.7-34), p=0.007, while ATG and also aGVHD grade III-IV, negatively impacted PFS, HR=2, 95%CI: 1.02-4.12, p=0.04, and HR=5.88, 95%CI: 1.7-20, p=0.005 respectively. Conclusion: We confirm that ECP is an effective treatment for GVHD in a good proportion of patients with overall response rate of 59%. Interestingly, we observed a better PFS in patients receiving ECP for longer time as in the case of chronic GVHD, which could be related to the GVL effect itself but also a possible involvement of the ECP. As patients with advanced phase of GVHD were poor responders, we suggest that an early use of ECP in the acute phase of the inflammation before organ damage, could lead to optimal results. Disclosures Michallet: Novartis: Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy. Nicolini:Incyte: Consultancy, Honoraria, Speakers Bureau; Sun Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

Graft Versus Host Disease (GVHD) Prophylaxis with Everolimus and Tacrolimus Is Associated with a High Incidence of Sinusoidal Obstruction Syndrome and Microangiopathy – Results of the EVTAC Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1172-1172
Author(s):  
Uwe Platzbecker ◽  
Malte Bonin ◽  
Eray Goekkurt ◽  
Joergen Radke ◽  
Alexander Kiani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Prophylactic Regimen ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

Abstract Beyond disease biology, the success of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies is mainly determined by the occurrence and extent of graft versus host disease (GVHD). Therefore, prevention of GVHD is the major goal and challenge in clinical HSCT. A calcineurin-inhibitor combined with methotrexate is the standard graft versus host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus is a derivative of sirolimus, which also seems to mediate anti-leukemia effects. Given the potential synergism and favourable toxicity profile of everolimus and tacrolimus (EVTAC) after allogeneic HSCT we sought to investigate the efficacy of this combination in patients with either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). We report a combination of everolimus (days 0–56) and Tacrolimus (from day −1 on) in 24 patients (pts, median age 62 years) with either MDS (n=17) or AML (n=7) undergoing intensive busulfan-based conditioning followed by HSCT from related (n=4) or unrelated matched (n=12) or 1-allele mismatched (n=8) donors. All pts engrafted and only one experienced grade IV mucositis. However, although everolimus was scheduled to be administered up to day 56, patients received the drug a median of 44 days (range 10–56) only. The reason for premature discontinuation (50%) were either occurrence of early-onset (day 6) GVHD associated hyperbilirubinemia CTC grade 4 (n=1), transplantation-associated microangiopathy (TMA, n=3), sinusoidal obstructive syndrome (SOS) of the liver (n=6) or a drop of platelets after engraftment by at least 50% (n=2). Nine pts (37%) developed grade II–IV acute GVHD, however, chronic extensive GVHD was observed in 11 of 17 (64%) evaluable pts. TMA occurred in 7 pts (29%) with two cases of acute renal failure. In five out of seven patients with TMA either tacrolimus (n=4) or everolimus (n=1) blood through levels were slightly above the upper target level at the time of TMA appearance. The study was terminated prematurely because additional 6 pts (25%) developed SOS, which was fatal in two cases. With a median follow-up of 26 months, the 2-year overall survival rate is 47%. In conclusion, although this new combination appears to be effective as prophylactic regimen for acute GVHD, the incidence of TMA and SOS seems to be higher compared to other regimens. As a result this combination cannot be recommended as prophylactic regimen after busulfan-based intensive conditioning. However, studies in the context of TBI-based or reduced-intensity conditioning regimens might come to a different conclusion.

Does Donor Epstein-Barr Virus (EBV) Seropositivity Affect Recipient's Risk of Graft Versus Host Disease (GVHD) in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5766-5766
Author(s):  
Erden Atilla ◽  
Esmanur Kaplan ◽  
Pinar Ataca Atilla ◽  
Selami Kocak Toprak ◽  
Pervin Topcuoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction: EBV seropositivity in general population is 80%. Reactivation of latent infection in pre-transplant seropositive patients causes post-transplant lenfoproliferative disease (PTLD) following Allo-HSCT. The effect of donor EBV positivity on recipient's risk of graft versus host disease is not clear. Our aim is to present EBV seroprevalence and PTLD incidence as well as demonstrating the relation of EBV seropositivity with GVHD. Patients and Methods: A total of 364 allogeneic stem cell transplant recipients and donors were evaluated retrospectively from 2006 to 2015. During Allo-HSCT preparation procedures all recipients and donors were serologically tested. EBV specific IgG (VCA-IgG, EBNAIgG, EA-IgG) and IgM (VCA-IgM) antibodies were determined by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). All patients were followed for reactivation. Results: EBV IgG positivity was detected in 338 of recipients (92.8%) and 283 of donors (77.7%). There was no statistically difference detected between related or unrelated transplants. The mean age was 37 (range 16-67). 217 recipients were male (60%). 295 (81%) patients were transplanted for malign hematological diseases. The majority of patients were grafted from full-matched related donors (258, 71%). The most common source of stem cell was peripheral blood in 299 patients (82%) followed by bone-marrow in 56 patients (15%), bone-marrow plus peripheral blood in 9 patients (3%). 273 (75%) patients received myeloablative conditioning regimen. All patients received prophylactic acyclovir (in related transplants 400mg 3 times daily, in un-related transplants 800mg 3 times daily) starting from conditioning and up to three months posttranplant period. One pretransplant seropositive 26 year-old aplastic anemia patient had PTLD with EBV IgM positivity within 3 months posttransplant. He received 4 cycles of rituximab and prednisolone and achieved complete response. Three patients had EBV IgM positivity in posttransplant 4, 9 and 24th months with symptoms of infectious mononucleosis. The seropositivity resolved without treatment. Acute GVHD developed in 223 patients (61%) whereas chronic GVHD was detected in 285 (78%) of patients. The incidence of acute GVHD was similar when donor was EBV seropositive compared to seronegative (78% vs 22%, p=0.72). Chronic GVHD incidence was similar between donor EBV seropositive group compared to seronegative group (80% vs 20%, P=0.199). Conclusion: EBV seropositivity is common detected in 92.8% of our allo-HSCT recipient cohort. Donor EBV status did not have an effect on developing acute or chronic GVHD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association between human leukocyte antigens and graft-versus-host disease occurrence after allogenic hematopoietic stem cell transplantation

2012 ◽  
Vol 130 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Daniela Máira Cardozo ◽  
Sofia Rocha Lieber ◽  
Silvia Barbosa Dutra Marques ◽  
Francisco José Aranha ◽  
Afonso Celso Vigorito ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.

Positive Impact of Chronic Graft-Versus Host Disease on Survival in 928 Allogeneic Hematopoietic Stem Cell Transplant Recipients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1952-1952 ◽  
Author(s):  
Gunhan Gurman ◽  
Pinar Ataca ◽  
Erden Atilla ◽  
Sinem Civriz Bozdag ◽  
Selami Kocak Toprak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Lower Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Immune Mediated

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a standard curative treatment option in hematological diseases. The anti-leukemic activity relies not only the effects of conditioning regimen but also the immune mediated graft-versus leukemia (GVL) effect. Donor T cells are responsible for the GVL and causes complications namely acute and chronic graft versus host disease (GVHD). Herein, we aim to present the relation of graft versus host disease with survival and relapse. Patients and Methods: We retrospectively evaluated 928 Allo-HSCT between 1989 and 2015 followed in our institution. Chi-square test and student's t test were used in comparison. P <0.05 was considered statistically significant. Results: 551 patients were male (59%) and 377 patients (41%) were female. The median age of the group was 34 (range 15 -71). Patients received stem cell from related donors more frequently (85%) with HLA full match (66%). Peripheral blood was the source of stem cells in 645 recipient (70%) followed by bone marrow (28%). 75 patients were diagnosed as benign hematological disorders. The most common malign hematological diagnosis was acute myeloid leukemia in 366 patients (39%). Patients received 80% of myeloablative conditioning regimen prior to transplantation. 43% of the patients diagnosed as acute GVHD and 45% had chronic GVHD. 798 achieved engraftment (86%) neutrophil engraftment median of 16 days, platelet engraftment median of 14 days. Relapse was detected in 6% of patients. The overall survival (OS) was 59 months and progression free survival (PFS) was 33 months. Acute GVHD had no impact on OS, PFS, relapse rate. The OS in patients with chronic GVHD was significantly higher than in GVHD negative patients (68.8 vs 56.9, P=0.009). Although chronic GVHD patients had lower risk of relapse and higher PFS, the results were not statistically significant. Conclusion: GVHD is a serious complication and important cause of post transplant morbidity. Chronic GVHD is associated with lower risk of relapse in previous studies. In this study, we have concluded the improved OS in patients with chronic GVHD. The immune mediated GVL effect may be the reason for anti-leukemia effect and improved survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcome of Children Developing Grade III-IV Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Report on Behalf of the EBMT Paediatric Diseases Working Party

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 76-76
Author(s):  
Alice Bertaina ◽  
Franco Locatelli ◽  
Anita Lawitschka ◽  
Adriana Balduzzi ◽  
Jean-Hugues Dalle ◽  
...  
Keyword(s):  
Stem Cell ◽  
Confidence Interval ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Number Of Children ◽  
Stem Cell Source ◽  
Grade Iii

Abstract Introduction Acute graft versus host disease (aGvHD) still remains one of the major causes of procedure-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Information on the outcome of paediatric patients experiencing this complication is limited. For this reason, we conducted a retrospective registry-based analysis on 2519 children who developed grade III-IV acute GVHD and were reported to the European Blood and Marrow Transplantation (EBMT) registry. Patients and methods Included in the study were children below age of 18 years who were transplanted between 2004 and 2014. Median year at transplantation was 2009. Of these children, 826 children had a non-malignant disorder, while 1689 were affected by malignancies. The donor was an HLA-identical sibling in 707 cases and an unrelated donor in 1081 cases. Umbilical cord blood (UCBT) was employed as stem cell source in 396 cases, while a relative other than a compatible sibling was utilized in 202 cases. Overall, 1281 patients were given bone marrow (BM), while 800 received peripheral blood stem cells (PBSC). Results Grade III acute GvHD occurred in 1607 patients (64% of the overall population), while grade IV acute GvHD was diagnosed in 908 (36%). Chronic GvHD occurred in 649 patients (26 % of the overall number of children who developed grade III-IV aGVHD). It was extensive in 333 (13%) and of limited severity in 269 (11%). At time of last follow-up, 1341 patients were alive (53%), while 1178 were dead (47 %). Fifty-seven patients were lost to the follow-up. Relapse of the original disorder occurred in 219 children (19.7% of patients experiencing grade III-IV aGvHD). Transplant-related causes were responsible for the death of 902 patients (76.5%), while 6 (0.5%) patients developed a secondary malignancy. The 3-year Kaplan-Meyer probability of overall survival (OS) was 46.7% (confidence interval 95, 44.1-49.5) and 50.9% (confidence interval 95, 47.1-54.9) in patients affected by malignant and non-malignant disorders, respectively. Patients who received as stem cell source BM had a better outcome in comparison to those who received PBSC (3-year OS, 53.2 vs 40.4%, P&lt;0.0001). In the overall cohort, in comparison to patients who developed limited cGvHD, the extensive form of the disease had a detrimental effect on the outcome, being the 3-year OS 74.2% and 41.6%, respectively (P&lt;0.0001). In multivariate analysis, the only variables affecting overall survival were the age at transplant (P&lt;0.0001) and the type of donor (sibling vs UD, CB, MMFD, P&lt;0.0001). The 3-year Kaplan-Meyer probability of non-relapse mortality (NRM) was 37.4% (confidence interval 95, 34.9-39.9) and 45.9% (confidence interval 95, 42-49.7) in malignant and non-malignant disorders, respectively. Also in this case, use BM instead of PBSC seems to be an advantage, being the 3-year NRM 35.1% and 47.8%, respectively. In multivariate analysis, besides the age at transplant (P&lt;0.0001) and the type of donor (sibling vs UD, CB, MMFD, P&lt;0.0001), the use of a myeloablative conditioning regimen (MAC) chemo-based (P&lt;0.0001) and the development of extensive chronic GvHD (P&lt;0.0001), had a detrimental effect on NRM. Conclusion These data indicate that the occurrence of grade III-IV aGVHD is associated with a dismal outcome also in paediatric patients. The main cause of fatality is represented by non-relapse mortality, while leukemia recurrence affected outcome of a lower number of children. Although the outcome of children experiencing grade III-IV aGvHD is improving over time, strategies aimed at preventing this immune-mediated complication and at optimizing its treatment are desirable. Disclosures Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding.

scholarly journals Elimination of Acute GvHD with Three Doses of Abatacept Prophylaxis Combined with Post-Transplant Cyclophosphamide after Myeloablative Treosulfan-Based Conditioning in the HLA Identical Sibling and Unrelated (10-12/12) Peripheral Blood Stem Cell Donor Setting: Improved Safety and Efficacy Compared to Alemtuzumab Prophylaxis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4540-4540
Author(s):  
Amit Patel ◽  
Jun Yong
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Safety And Efficacy ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Secondary Outcomes ◽  
Cmv Reactivation

Background. Acute graft versus host disease (GvHD) remains a major cause of treatment failure post allogeneic stem cell transplantation (HSCT). CD28-CD80/CD86 axis T cell co-stimulation blockade with CTLA4-Ig using abatacept (AB) is an emerging acute GvHD prophylaxis strategy1. After myeloablative conditioning (MAC), together with methotrexate and calcineurin inhibition, four doses of AB commencing day (d)-1 is being investigated in the unrelated HLA 7/8 and 8/8 mismatched/matched donor settings, mostly in children2. It is unknown if AB can be de-escalated in adults to three doses for HLA matched sibling (SIB) or unrelated 10-12/12 donors (MUD), or combined with post-transplant cyclophosphamide (PT-CY) GvHD prophylaxis3, or combined with treosulfan (TREO)-based MAC4, which are other emerging transplant strategies. We investigated the safety and efficacy of this combination, and compared outcomes to a standard anti-CD52 directed IgG1 alemtuzumab (CH) prophylaxis regimen5 in a reduced intensity conditioning (RIC). Methods. We report a single centre consecutive cohort study using peripheral blood stem cells from SIB or HLA 10-12/12 MUDs, for HSCT in adults with blood cancer indications (intuitional registration: 1920-31). One group received AB GvHD prophylaxis while the other group received CH. During 2018-2019, the AB cohort received MAC with IV fludarabine 150 mg/m2, IV TREO 42 mg/m2, and 2 Gy total body irradiation (TBI). GvHD prophylaxis comprised three doses of IV AB 10 mg/kg on d+5, +14, and +28. This was combined with IV PT-CY 50 mg/kg on d+3 and +4, IV tacrolimus 0.03 mg/kg/d infusion from d+5, and IV mycophenolate mofetil 15 mg/kg tds from d+53. The MAC AB cohort was compared to a RIC CH cohort, chosen to be biased against AB. During 2017-2018 the CH cohort received RIC with IV fludarabine 150 mg/m2and IV melphalan 140 mg/m2. GvHD prophylaxis comprised IV CH 10 mg on d-7 to d-3, and IV ciclosporin 1.5 mg/kg bd from d-1. The primary outcome measure was the incidence of acute GvHD6 at d100 and 180 post HSCT. Secondary outcomes measures were the incidence of graft failure, mixed donor chimerism, donor lymphocyte infusion (DLI), CMV reactivation, relapse, overall survival, at d100 and 180. The AB and CH cohorts were indirectly compared. Results. A total of 39 patients were included in this study, with 15 consecutive patients in the AB group (Table). The AB group had a median Karnofsky score of 70% and HCT-CI of 6; significant comorbidity greater than other reports1,2. The major cancer indications were acute leukaemia and myelodysplastic syndrome (MDS). The AB and CH groups were largely balanced. There were no AB related infusion reactions. As expected for MAC, the AB group had a numerically but not clinically significantly slower time to engraftment relative to the RIC CH group. There was no AB group graft failure. Remarkably, the AB group did not experience acute GvHD compared to the CH group by d100 (P=0.03) and d180 (P<0.01). In contrast, by d100, 29% in the CH group experienced acute GvHD after a median of 59 days post HSCT. No AB group patients experienced mixed donor chimerism (P<0.01), nor required a DLI (P<0.01) compared to the CH group, where all had <99% T cell or whole blood values at d100. Consequently, 45% of the CH cohort without acute GvHD were treated with DLI, with all patients experiencing acute GvHD at a median of 39 days post DLI (Table). Other secondary outcomes were similar. The AB group experienced a CMV reactivation rate of 67% in IgG seropositive patients. Unfortunately, 93% of CMV IgG positive patients in the CH group experienced CMV reactivation. No relapses were observed by d180 in the AB group, whereas in the CH group, 8% of patients experienced relapse. Mortality at d180 was 20% in the MAC AB group, and 21% in the RIC CH group. Conclusions. Acute GvHD prophylaxis with only three doses of AB and PT-CY post TREO-based MAC appears to be safe and efficacious in the SIB and MUD settings, in a highly co-morbid adult blood cancer population. This AB approach seems favourable compared to CH despite RIC, where acute GvHD without DLI or post DLI remains significant. A prospective multicentre clinical trial with AB in this setting seems warranted to confirm these remarkable findings of patient benefit. References. 1. Biol Blood Marrow Transplant (BBMT) 2013;19:1638-49. 2. NCT01743131. 3. Lancet Haematol 2019;6:e132-43. 4. Cancer 2017;123:2671‐79. 5. BBMT 2017;23:805-12. 6. BBMT 2016;22:4-10. Table Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Abatacept, alemtuzumab, cyclophosphamide all the for the indication of graft versus host disease (GvHD) prophylaxis.

scholarly journals Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

2020 ◽  
Vol 29 ◽  
pp. 096368972096590
Author(s):  
Chutima Kunacheewa ◽  
Weerapat Owattanapanish ◽  
Chutirat Jirabanditsakul ◽  
Surapol Issaragrisil
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Free Survival ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Matched Sibling

Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has resulted in inferior outcomes in matched sibling donor (MSD) employing peripheral blood (PB) SCTs. We hypothesized that adding thymoglobulin to PTCy would be able to control GvHD effectively. We retrospectively compared the use of standard GvHD prophylaxis encompassing a combination of PTCy and thymoglobulin (ATG) in patients with myeloid malignancies in a myeloablative conditioning MSD PBSCT. Forty-two patients underwent PBSCT using either methotrexate and cyclosporine (MTX/CSA, 21 patients) or PTCy and ATG (21 patients) as a GvHD prophylaxis. With median follow-ups of 71 months, the 1-year GvHD-free, relapse-free survival rates and chronic GvHD-free survival rate of the standard and PTCy/ATG groups were similar: 24% versus 37% ( P = 0.251) and 29% versus 43% ( P = 0.095), respectively. When focusing on chronic GvHD we observed that 17/35 patients (48.6%) suffered from this, 5/18 (27.8%) treated with MTX/CSA had extensive chronic GvHD, but 0/17 PTCy/ATG did. Twenty-one patients required additional GvHD treatment; 7/21 in the PTCy/ATG received only corticosteroid, while 8/14 MTX/CSA required at least 2 drugs. The 5-year overall survival rates were 52% and 52% ( P = 0.859), and the 5-year disease-free survival rates were 52% and 52% ( P = 0.862) for the MTX/CSA and PTCy/ATG groups, respectively. We conclude that PTCy in combination with ATG without immunosuppression of a calcineurin inhibitor can effectively control GvHD.

Selective Depletion of Alloreacting CD25+ Cells from Stem Cell Allografts Can Reduce Acute Graft-Versus-Host Disease Following Matched Related Donor Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 426-426
Author(s):  
Scott R. Solomon ◽  
Thao Tran ◽  
Charles S. Carter ◽  
Nancy Hensel ◽  
Laura Wisch ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Cell Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Donor T Cells ◽  
Related Donor

Abstract Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplant (SCT), especially in older patients. We previously showed that host-reactive donor T cells are selectively depleted (SD) from an allograft ex vivo, following a short co-culture of donor cells with irradiated T cell stimulators from the recipient and subsequent treatment with an anti-CD25 immunotoxin. We report a pilot study to test the hypothesis that GVHD could be decreased in a cohort of elderly patients receiving SD allografts from HLA-identical sibling donors. Sixteen patients, median age 65 years (range 51–73), with advanced hematologic malignancies were transplanted following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n=5), melphalan (n=5), or busulfan (n=6). Cyclosporine was used as the only additional GVHD prophylaxis. SD allografts contained a median CD34 dose of 4.5x106/kg (range 3.5–7.3) and an SD CD3 dose of 1.0x108/kg (range 0.2–1.5). Fifteen patients achieved sustained engraftment. The helper T lymphocyte precursor (HTLp) frequency assay demonstrated depletion of host-reactive donor T cells in 9/11 cases tested from a mean of 1/182,089 to 1/822,354 (mean 5.5-fold depletion), while third party responses were conserved. Kaplan-Meier estimates of probability of grade II-IV and grade III-IV acute GVHD were lower than those seen in a historical control group of patients receiving cyclosporine alone for GVHD prophylaxis (35±13% vs. 57±10%, p=0.34) and (7±6% vs. 38±6%, p=0.05), respectively. Of note, the two patients who developed visceral (gut ± liver) GVHD showed ineffective allodepletion by HTLp (figure). Chronic GVHD occurred in five of 14 evaluable patients. At a median follow-up of 212 days (range 60 – 690), seven of sixteen patients remain alive and in remission. Relapse deaths occurred in four patients (refractory AML [2], therapy-related MDS [1], and CMML [1]). Non-relapse mortality in this high-risk cohort of patients included graft failure [1], GVHD [2], infection [1], and myocardial infarction [1]. In summary, CD25-directed allodepletion of stem cell allografts can reduce clinically relevant acute GVHD following matched related donor transplantation. Figure Figure

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