Allogeneic STEM CELL Transplants for Patients with Myelofibrosis: Changes in the Transplant Platform and Improved the Outcome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4336-4336
Author(s):  
Stefania Bregante ◽  
Alida Dominietto ◽  
Anna Ghiso ◽  
Anna Maria Raiola ◽  
Francesca Gualandi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Older Age ◽  
Recent Period ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Recent Group ◽  
Alternative Donor ◽  
Matched Sibling ◽  
Time Periods

Abstract Introduction. Allogeneic stem cell transplantation remains the only curative therapy for patients with myelofibrosis, but is associated with relevant morbidity and mortality, possiby due to the specific nature of the disease. The outcome is significantly worse when alternative donor transplants are compared to matched siblings (MSD): in a recent cooperative study, TRM was 22% in MSD vs 59% in patients receiving unrelated donor grafts (UD) (Blood 2014 124:1183). Aim of the study. This is a retrospective analysis of 95 patients with myelofibrosis (MF) allografted in our Unit between 2001 and 2014. The aim of the study was to assess whether (a) the outcome of alternative donor grafts has improved with time and (b) how this compares with the outcome of identical sibling grafts. Patients were studied in two time intervals-2000-2010 (n=58) and 2011-2014 (n=37). The DIPSS score was comparable in the two time periods, but differences in the most recent group included older age (58 vs 53 years, p=0.004), more family haploidentical donors (54% vs 5%, p<0.0001), and the introduction of the thiotepa- fludarabine- busulfan conditioning regimen (70% of patients vs 2%, p<0.0001). Reduced intensity regimens were used mainly in the first transplant period (85% vs 30% in the most recent period). All patients received unmanipulated grafts (86% bone marrow). GvHD prophylaxis for sibling donor grafts was cyclosporin methotrexate (CsA+MTX), with the addition of ATG for unrelated transplants. Haploidentical grafts were performed with high dose cyclophosphamide post-transplant (PT-CY), CsA and mycophenolate. Results. Acute and chronic GvHD were comparable in the two time periods. Full donor chimerism was >90% in both periods in sibling transplants; on the other hand, in alternative donor transplants it improved from 69% to 95% in the most recent period (p=0.02). The 3 year transplant related mortality (TRM), in the 2011-2014 vs the 2000-2010 period, is 16% vs 38% (p=0.08), the relapse rate 19% vs 43% (p=0.01) and actuarial survival 70% vs 39% (p=0.08). Improved survival was most pronounced in alternative donor grafts (69% vs 21%, p=0.02), as compared to matched sibling grafts (72% vs 45%, p=0.4). The actuarial 3 year survival for high risk DIPSS was 8% in the 2000-2010 period, and it is currently 57% (p<0.01). In multivariate Cox analysis, DIPSS (p=0.001) and transplant score (transfusion requirement and spleen size) (p=0.03) were independent predictor of survival. Donor type was not predictive in multivariate analysis. Conclusions. The outcome of allografts for myelofibrosis has improved in recent years, due to a reduction of both TRM and relapse, despite comparable DIPSS and older age in the more recent group of patients. Improved survival has been more pronounced for alternative donor transplants, such that 3 year survival is currently superimposable to sibling donor grafts. There have been significant changes in the transplant platform, including conditioning regimen, donor type and GvHD prophylaxis, mainly with the introduction of PT-CY. All of our MF patients now receive the thiotepa, busulfan fludarabin conditioning, and, for patients lacking a matched sibling, a family haploidentical donor seems to be an interesting alternative. Disclosures No relevant conflicts of interest to declare.

Second Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for Relapse of Hematological Malignancies after First Allo-HSCT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3947-3947 ◽  
Author(s):  
Koji Kato ◽  
Toshihiro Miyamoto ◽  
Koji Yonemoto ◽  
Naoyuki Uchida ◽  
Hiroyasu Ogawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Alternative Donor ◽  
Relapsed Disease ◽  
Donor Source

Abstract [Background] Patients with hematological malignancies who relapse after their first allogeneic hematopoietic stem cell transplantation (allo-HSCT1) have a dismal prognosis. Second allo-HSCT (allo-HSCT2) with bone marrow or peripheral blood stem cell from matched related or unrelated donor has been already used as a potentially curative treatment. Furthermore, umbilical cord blood (UCB) or haplo-identical transplantation as allo-HSCT2 has been increasingly used, because rapid availability of UCB or haplo-identical transplantation may provide a great advantage for patients who need urgent allo-HSCT2 to treat aggressive relapsed disease after allo-HSCT1. However, there is limited information of alternative donor sources on the efficacy of allo-HSCT2. [Methods] Data from the Japan Society for Hematopoietic Cell Transplantation database were retrospectively analyzed. [Results] A total of 1150 patients with hematological malignancies had received allo-HSCT1 after January 2000 and subsequently received allo-HSCT2 for their relapsed or refractory disease until December 2011. The median interval between allo-HSCT1 and allo-HSCT2 was 368 days (range: 17-4028). Patients had acute myeloid leukemia (AML, n = 683), myelodysplastic syndrome (MDS, n = 62), acute lymphoblastic leukemia (ALL, n = 275), malignant lymphoma (ML, n = 61), chronic myeloid leukemia and myeloproliferative disease (CML/MPD, n = 32), and other diseases (multiple myeloma/adult T-cell leukemia/chronic lymphocytic leukemia, n = 37). The intensity of the conditioning regimen was classified as full-intensity conditioning in 171 patients (15%) and reduced-intensity conditioning in 979 patients (85%). The number of mismatches was counted among HLA-A, HLA-B (low-resolution typing), and DRB1 (high-resolution typing). Donors at allo-HSCT2 were HLA-matched or 1 antigen HLA-mismatched related donor (MRD, n = 116), unrelated bone marrow donor (URD, n = 339), single-unit UCB (n = 515), and 2 antigens or more HLA-mismatched donor (mmRD, n = 180). Anit-thymoglobulin (ATG) was administered for GVHD prophylaxis in 125 patients (70%) of patients with mmRD. Among 1150 patients, 242 (21%) were alive with a median follow-up period of 628 days (range, 0-3627). The 2-year overall survival (OS) and progression-free survival (PFS) rate were 19.8% [95% confidence interval (CI), 17.5-22.5%] and 19.1% (95% CI, 16.7-21.7%), respectively. The cumulative incidence of relapse and transplant-related mortality (TRM) at 2-year were 40.4% (95% CI, 37.5-43.4%) and 40.4% (95% CI, 37.5-43.4%), respectively. Confounding factors that might affect OS were as follows: age, gender, disease, disease status at allo-HSCT2, intervals from allo-HSCT1 to allo-HSCT2, date at transplantation, conditioning regimen, donor source, and GVHD prophylaxis. Multivariate analysis revealed that higher OS correlated with complete remission/partial remission/chronic phase in disease status at allo-HSCT2 [hazard ratio (HR) 0.55, 95% CI 0.47-0.66; P < 0.001], longer interval (>12 months) between allo-HSCT1 and allo-HSCT2 (HR 0.68, 95% CI 0.47-0.78; P < 0.001), and CML/MPD (HR 0.56, 95% CI 0.36-0.87; P = 0.010). In contrast, mmRD without ATG was associated with inferior OS (HR 1.55 to MRD, 95% CI 1.17-2.06; P = 0.003). The OS at 2 years according to donor source was as follows: 18.0% in MRD, 28.2% in URD, 18.1% in UCB, 12.5% in mmRD with ATG, and 5.5% in mmRD without ATG. [Conclusions] Allo-HSCT2 is a potential curative therapy especially in patients who have a sensitive disease and an interval time of >12 months to allo-HSCT2 even after allo-HSCT1, whereas the outcomes of allo-HSCT2 from alternative donor sources such as URD, UCB, and mmRD with ATG are comparable to that of MRD. Overall, the outcome of allo-HSCT2 has been still unsatisfactory because of the high rate of TRM and relapse. Novel strategy is required to further improve the outcome of allo-HSCT2, particularly for patients with refractory or relapsed disease despite allo-HSCT1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparison of Matched-Sibling Donors Versus Unrelated Donors in Allogeneic Stem Cell Transplantation (allo-SCT) for Primary Refractory Acute Myeloid Leukemia (PRF AML): A Report of 1041 Patients from the Acute Leukemia Working Party of the EBMT

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 196-196
Author(s):  
Eolia Brissot ◽  
Myriam Labopin ◽  
Matthias Stelljes ◽  
Gerhard Ehninger ◽  
Gernot Stuhler ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Predictive Factors ◽  
Research Funding ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Factors Associated ◽  
Donor Type ◽  
Unrelated Donors ◽  
Matched Sibling

Abstract Background: PRF-AML is associated with a dismal prognosis. Approximately one third of patients younger than 60 years, and 50 % of older patients, with newly diagnosed AML, fail to achieve complete remission (CR) with standard induction chemotherapy. Allo-SCT in the setting of active disease is an alternative strategy. The increased availability of unrelated donors (UD) together with the use of reduced-intensity conditioning (RIC) regimens have opened the possibility for transplantation to a larger number of patients in comparison to standard myeloablative regimens (MAC). Because of the high risk of allo-SCT in this setting, there are still questions on the patient outcome depending on the donor type. Aims: The current study aimed to compare the outcomes of allo-SCT from matched sibling donors (MSD) (n=660) vs UDs (n=381), for patients with PRF AML. Methods: The major endpoints were to assess overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and non relapse mortality (NRM). Results: 660 patients received a MSD, 296 patients a matched UD (10/10) and 85 a mismatched UD (9/10), respectively. Median age was higher in the UD group (50.5 yrs (18-74) vs 47.7 yrs (18-74), p=0.006). The median time from diagnosis to allo-SCT was similar (110 days [60-180] in the MSD group vs 111days [60-178] in the UD group; p=0.33). In the MSD allo-SCT, 57 % received a MAC regimen, 29% a RIC regimen, and 14% a sequential conditioning regimen; while, in the UD transplants, 44.4 % received a MAC regimen, 24.4% a RIC regimen, and 31.2% a sequential conditioning regimen (p<10-4). Peripheral blood stem cell (PBSC) was the main stem cell source (92% in the MSD allo-SCT vs 94.8% in the UD allo-SCT, p=0.09). Median follow-up was statistically longer in the UD group than in the MSD group (19 months [range, 1.5-143] vs 16 months [2-153], respectively, p=0.04). In univariate analysis, LFS at 2 years was 25.3% in MSD group vs 28.3% in UD group (p=0.56) (Fig.1). In multivariate analysis, 2 predictive factors were associated with lower LFS: cytogenetics (poor vs intermediary; HR=1.61, 95%CI,1.24-2.09, p=0.0004) and time from diagnosis to transplant (above the median 110 days) (HR=1.21, 95%CI,1.02-1.44, p=0.03), whereas Karnofsky status at transplant ≥90% (KS) was associated with better LFS (HR=0.67, 95%CI,0.56-0.80, p=0.0001). In univariate analysis, OS at 2 years was comparable in both groups (30.9% in MSD group vs 34.3% in UD group (p=0.57)) (Fig2). In multivariate analysis, 4 predictive factors were associated with lower OS: age>50 yrs, cytogenetics, time from diagnosis to transplant and CMV positive status whereas Karnofsky status at transplant ≥90% (KS) was associated with better OS. 71% patients with a MSD and 68.6% patents with an UD reached CR after allo-SCT (p=0.73). In univariate analysis, RI at 2 years was 53.7% in MSD group and 56.4% in UD group, respectively (p=0.038). In multivariate analysis for RI, cytogenetics and time from diagnosis to transplant were the only risk factors associated with increased relapse [(HR=1.74, 95%CI,1.30-2.33, p=0.0002) (HR=1.29, 95%CI,1.06-1.58, p=0.01), respectively] whereas KS was a protective factor (HR=0.77, 95%CI,0.62-0.95, p=0.01). The incidence of aGVHD≥2 was higher in UD group (35.5% vs 27.9%, p=0.012). At 2 years, the cumulative incidence of chronic GVHD (cGVHD) was not statistically different between MSD and UD (28.9% and 25.8%, respectively, p=0.56) (univariate analysis). As for, NRM at 2 years, there was not statistical difference between MSD and UD groups (21% vs 25.1%, p=0.112). In multivariate analysis, patient age (>50 yrs) and CMV positive status were factors associated with higher NRM (HR=1.77, 95%CI, 1.27-2.47, p=0.001; HR=1.68, 95%CI, 1.14-2.47, p=0.008), while RIC regimen compared to MAC regimen was the only factor associated with lower NRM (HR=0.59, 95%CI, 0.41-0.85, p=0.005). Conclusion Allo-SCT may rescue one third of patients with primary refractory AML. Importantly, the donor type did not have any impact on PRF patients' outcomes. In contrast, time to transplant was a major prognostic factor for LFS and OS. For patients with PRF AML, that do not have a matched sibling donor, allo-HST from UD is a suitable option and thus initiation of an early search and allocating of a suitable donor is therefore indicated. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Finke: Riemser: Research Funding, Speakers Bureau; Neovii, Novartis: Consultancy, Research Funding, Speakers Bureau; Medac: Research Funding. Esteve:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Mohty:Janssen: Honoraria; Celgene: Honoraria.

Matched Related vs Alternative Donor Stem Cell Tranplantation (SCT) for Diamond Blackfan Anemia: A Report from the Diamond Blackfan Anemia Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2063-2063 ◽  
Author(s):  
Adrianna Vlachos ◽  
Eva Atsidaftos ◽  
Jeffrey M. Lipton
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Osteogenic Sarcoma ◽  
Red Cell ◽  
Myeloablative Conditioning ◽  
Diamond Blackfan Anemia ◽  
Alternative Donor ◽  
Matched Sibling

Abstract Background: Diamond Blackfan anemia (DBA) is a rare disorder characterized by red cell aplasia, congenital anomalies and a predisposition to cancer. Corticosteroids and red cell transfusions are the mainstays of therapy. Hematopoietic stem cell transplantation is curative in DBA, however its role in these patients is controversial. Purpose: The purpose of this report is to review the outcome and treatment-related morbidity for HLA matched sibling versus alternative donor SCT for DBA patients enrolled in the Diamond Blackfan Anemia Registry (DBAR). Methods: The DBAR is a comprehensive database of patients with DBA who are enrolled after informed consent is obtained. The patients, their families, and their physicians complete a detailed questionnaire. A review of medical records and telephone interviews are performed to complete and clarify the information provided. Results: As of May 1, 2005, 420 patients have been enrolled in the DBAR, 36 of which have met the criteria for the diagnosis of DBA and have undergone an allogeneic HLA-matched sibling or alternative donor SCT. The median age at SCT for all patients was 7 years 10 months; 7 years 4 months versus 9 years 8 months for the 21 HLA-matched sibling and 15 alternative donor SCT, respectively. The major indication for SCT was transfusion dependence. In addition, two patients developed severe aplastic anemia and one significant thrombocytopenia. The majority of HLA-matched sibling transplants were done using a non-irradiation-containing conditioning regimen. One patient undergoing an HLA-matched umbilical cord SCT using a non-myeloablative conditioning regimen is engrafted but too early to evaluate. The majority of alternative donor transplants were performed using total body irradiation. One unrelated bone marrow transplant recipient also underwent non-myeloablative conditioning and is fully engrafted one year post-transplant. Sixteen of the 21 HLA-matched sibling donor transplants are alive and well, 4 of the failures occurring in patients older than 10 years of age (11, 12, 12 and 22 years) from interstitial pneumonia of unknown etiology, uncharacterized infection, veno-occlusive disease (VOD) of the liver and, in a heavily iron-overloaded patient with hepatitis C, adenovirus pneumonia, respectively. A 21 month old died from VOD. Of the 15 alternative donor SCT, one patient received bone marrow from a 3/6-mismatched sibling; another patient received a 5/6-mismatched parental bone marrow; 8 received unrelated bone marrow; 4 unrelated cord blood; and 1 unrelated peripheral blood stem cells. Three of these 15 patients are alive. The survival for allogeneic sibling versus alternative donor SCT is 72.7% ± 10.7% versus 19.1% ± 11.9% at greater than 5 years from SCT (p=0.01) (excluding a patient with osteogenic sarcoma diagnosed after SCT) or 17.1% ± 10.8% (including the osteogenic sarcoma patient, p=0.012). For patients under 10 years of age, the survival for allogeneic sibling versus alternative donor SCT is 92.3% ± 7.4% and 16.7% ± 14.8%, respectively, at greater than 4 years from SCT (p=0.01). Conclusions: The best outcomes for stem cell transplantation in DBA patients occur when performed prior to the age of 10 years, using HLA-matched sibling donors. Given the poor survival with alternative donor SCT, these transplants should be reserved only for those DBA patients with other complications requiring transplantation, i.e. aplastic anemia, red cell allosensitization or leukemia.

scholarly journals Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaime Sanz ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Moiseev Ivan Sergeevich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Matched Sibling ◽  
The Impact

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

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.

scholarly journals Improved Outcomes in Patients with Thalassemia Major Transplanted with Peripheral Blood and Marrow Grafts in Comparison with Cord Blood and Bone Marrow Grafts from Sibling Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 847-847
Author(s):  
Qiao chuan Li ◽  
Jian ming Luo ◽  
Zhong ming Zhang ◽  
Lian jin Liu ◽  
Ling ling Shi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Graft Rejection ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Matched Sibling

Abstract Background: Thalassemia major (TM) is a fatal genetic disease currently only curable with allogeneic stem cell transplantation. This is limited by the lack of suitable donors and the quantity of collected stem cells, and is often complicated by graft rejection and graft versus host disease (GVHD). Methods: The aim of the study was to compare the outcomes of TM patients transplanted with matched sibling cord blood (CB) and bone marrow (BM) grafts vs. matched sibling peripheral blood (PB) stem cell and BM grafts. The trial was designed as a prospective, open-label, single-center clinical protocol, where 204 TM patients were enrolled between January 2007 and November 2015 and transplanted with either PB + BM (n=99) or CB+BM (n=105), from an HLA-identical sibling donor. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and was registered at the Chinese Bone Marrow Transplant Registry (CBMTR). The primary end point was 2-year thalassemia free survival(TFS). Secondary end points included 2-year overall survival (OS), the cumulative incidence of GVHD, transplant related mortality (TRM), graft rejection (GF).The conditioning regimen were:1) busulphan (BU) (1.25 mg/kg) given orally four times per day for 4 days or 1mg/kg given intravenously (IV) four times per day for 4 days (day -9 to day -6); 2) fludarabine (FLU) (50mg/m2/day) given IV for 3 days (day -12 to day -11); 3) cyclophosphamide (CTX) (50 mg/kg/day) given IV for 4 days (day -5 to day -4); 4) anti-thymocytes globulin (ATG, Genzyme ) (2.5 mg/kg/day) given IV for 4 days (days -4 and day -1). All patients were placed on 30 mg/kg hydroxyurea orally once daily for 2-3 months before transplantation.GVHD prophylaxis consisted of a combination of cyclosporin A, methotrexate and mycophenolate mofetil regimen. [BMT 2009; 43(1):61-67]. Results : Patient and donor characteristics, and transplantation outcomes are listed in Tables 1 and 2, respectively. Data cut off for survival follow-up was March 31, 2016. The median follow-up time was 26 months (range, 4 months -105 months). Both neutrophil as well as platelet engraftment occurred significantly faster in the PB+ BM group than the CB+BM group (11 days vs. 13 days, P=0.001 and 15 days vs. 25 days, P=0.001, respectively). The rate of GF was the same in both groups (1.0%). The cumulative incidence of grade II-IV acute (a) GVHD and extensive chronic (c)GVHD in the PB+ BM group was higher than the CB+BM group: aGVHD=15.5% vs 1.0%, P=0.001; cGVHD= 6.4% vs. 0%, P=0.013. The cumulative rates of TRM at 2 years remained significantly lower in the PB+BM group compared to the CB+BM group with 2.0% and 12.5%,(P=0.005), respectively . Both OS and TFS at 2 years favored the PB +BM group compared to the CB+BM group : OS=98% vs. 86.5%,P=0.003;TFS= 97% vs. 86.5%, P=0.008.(Fig 1) Conclusion: Our results demonstrate that grafts composed of PB + BM had superior overall outcomes compared to CB + BM grafts, as evidenced by faster engraftment and lower TRM of the former despite substantially lower aGVHD and cGVHD rates of the latter. The mixed stem cell populaitons and the high cell dose achieved with the use of 2 different graft sources, toghether with the conditioning regimen used likely contributed to the superior outcomes seen with this regiem. This strategy could be of great benefit for the treatment of patient with TM and other benign hematologic disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Peritransplant Ruxolitinib Administration is Safe and Effective in Patients with Myelofibrosis: a Pilot Open-Label Study

2021 ◽  
Author(s):  
Haris Ali ◽  
Ni-Chun Tsai ◽  
Timothy Synold ◽  
Sally Mokhtari ◽  
Weimin Tsai ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Pilot Trial ◽  
Conditioning Regimen ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Grade 3

We report results of our prospective pilot trial (NCT02917096) evaluating safety/feasibility of peri-transplant administration of ruxolitinib for myelofibrosis treatment. Primary objectives were to determine the safety and identify maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was given at two dose levels (DL) of 5 and 10mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus GVHD prophylaxis. We enrolled 6 and 12 patients in DL-1 and DL-2, respectively. Median age at transplant was 65 years (range:25-73) for all patients. Per DIPSS, 4 patients were at high and 14 were at intermediate risk. PBSCs was the graft source from a matched sibling (n=5) or unrelated (n=13) donor. At each DL one patient developed DLTs: Grade 3 cardiac and GI with Grade 4 pulmonary in DL-1 and Grade 3 kidney injury in DL-2. All patients achieved engraftment. Cumulative incidence (CI) of acute GVHD grade 2-4 and 3-4 were 17% (95% CI: 6-47) and 11% (95% CI: 3-41), respectively. CI of 1-year chronic GVHD was 42% (95% CI: 24-74). With the median follow-up of 22.6 months (range:6.2-25.8) in surviving patients the 1-year overall and progression free survival were 77% (95% CI: 50-91) and 71% (95% CI: 44-87), respectively. Causes of death (n=4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results showed that peri-HCT ruxolitinib was safe and well-tolerated with the MTD determined as 10 mg BID, associated with dose-dependent PK and cytokine profile. The early efficacy data are highly promising in this group of high-risk older patients with MF.

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.

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