No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1739-1745 ◽  
Author(s):  
Mats Remberger ◽  
Oolle Ringdén ◽  
Igor-Wolfgang Blau ◽  
Hellmut Ottinger ◽  
Bernhard Kremens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Disease Free

Abstract The clinical results in 107 patients receiving a peripheral blood stem cell (PBSC) graft mobilized by granulocyte colony-stimulating factor (G-CSF) from HLA-A, -B, and -DR–compatible unrelated donors were compared to 107 matched controls receiving unrelated bone marrow (BM) transplants. Engraftment was achieved in 94% of the patients in both groups. The PBSC graft contained significantly more nucleated cells, CD34+, CD3+, and CD56+ cells (P < .001), and resulted in a significantly shorter time-to-neutrophil (15 versus 19 days) and platelet engraftment (20 versus 27 days), compared to the BM control group (P < .001). Probabilities of acute graft-versus-host disease (GVHD) grades II to IV were 35% and 32% (not significant [NS]) and of chronic GVHD 61% and 76% (NS) in the PBSC and BM groups, respectively. There was no difference between the 2 groups in bacteremia, cytomegalovirus reactivation or disease, and fungal infection. The 3-year transplant-related mortality (TRM) rates were 42% in the PBSC group and 31% in the BM controls (P = .7) and the survival rates were 46% and 51%, respectively. The probability of relapse was 25% and 31% in both groups (NS), resulting in disease-free survival rates of 43% in the PBSC group and 46% in the BM controls (NS). In the multivariate analysis, early disease, acute GVHD grade 0 to I, and presence of chronic GVHD were independent factors associated with a better disease-free survival in this study. PBSC from HLA-compatible unrelated donors can be used safely as an alternative to BM for stem cell transplantation.

Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2043-2051 ◽  
Author(s):  
Craig Kollman ◽  
Craig W. S. Howe ◽  
Claudio Anasetti ◽  
Joseph H. Antin ◽  
Stella M. Davies ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Donor Age ◽  
Free Survival ◽  
Unrelated Donors ◽  
Donor Characteristics ◽  
Disease Free

The National Marrow Donor Program (NMDP) maintains a registry of approximately 4 million volunteer unrelated donors for patients in need of a stem cell transplant. When several comparably HLA-matched volunteers are identified for a patient, various criteria are used to select a donor. A retrospective analysis of 6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was conducted to study the effects of various donor characteristics on recipient outcome. The evaluation addressed possible effects of donor age, cytomegalovirus serologic status, ABO compatibility, race, sex, and parity on overall and disease-free survival, acute and chronic graft-versus-host disease (GVHD), engraftment, and relapse. Age was the only donor trait significantly associated with overall and disease-free survival. Five-year overall survival rates for recipients were 33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P = .0002). A similar effect was observed among HLA-mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between recipient and donor did not affect outcome. The cumulative incidences of grade III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P = .005). The corresponding incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P = 0.02). Recipients with female donors who had undergone multiple pregnancies had a higher rate of chronic GVHD than recipients with male donors (54% versus 44%;P < .0001). The use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation. Age should be considered when selecting among comparably HLA-matched volunteer donors.

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.

Impact of Chronic Graft Versus Host Disease in the Overall Survival and Disease Free Survival of Patients with Hematologic Disorders Submitted to Allogeneic Bone Marrow Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4305-4305
Author(s):  
Emmerson de Sousa Eulalio ◽  
Elizabeth Schulz ◽  
José Salvador Rodrigues de Oliveira
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Graft Versus Host Disease ◽  
De Novo ◽  
Disease Free Survival ◽  
Extensive Form ◽  
Free Survival ◽  
Graft Versus Host ◽  
The Mean ◽  
Disease Free

Abstract The management of the chronic graft versus host disease (C-GVHD) in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still challenging and does not follow a consensus. This disease can manifest as auto-immune phenomena, often affecting multiple organs, and it is considered as a determinant factor for higher post transplant mortality and detrimental quality of life, although conversely associated with a strong graft versus tumor effect which determines a beneficial biological response in patients with haematological pathologies. The aim of this study was to determine the impact of the C-GVHD in the overall survival (OS) and disease free survival (DFS) in patients with hematologic pathologies who underwent allo-HSCT with HLA identical donors in the BMT Hospitals Sao Paulo and Santa Marcelina, in Sao Paulo, Brazil. We performed a retrospective study of historical cohort including 233 allo-HSC transplants, 151 patients aged 9 to 63 years old (median 31) with survival superior to 100 days, from August 1993 to December 2004. The classification of DECH-C followed the criteria of Seattle (Shulman et al. 1980) revised by Lee et al (2003). Our series was composed of 97 patients with chronic myeloid leukemia (CML), 54 with acute leukemias (AL), 42 with marrow failure (MF) and 40 with lymphoproliferative diseases (LPD). Forty one percent of the patients exhibited the advanced disease at HSCT time and the main source of HSC was bone marrow (n=174, 74.7%). The diagnosis of C-GVHD was performed in 166 procedures (71.2%). Seventy one patients (42.8%) were classified as C-GVHD quiescent, 69 (41.6%) as de novo, and 25 (15.1%) as progressive. The extensive form occurred in 95 cases (57.2%) and the limited form in 70 cases (42.2%). The mean OS for our cohort was 34.5 months (m) and the mean DFS was 29.5 m. The mean OS of patients with C-GVHD was 42 m, significantly higher than than 33.8m OS of patients without C-GVHD (p=0.05). Similarly, the DFS was 38.6m for C-GVHD patients, against 22.6m of DFS for patients without C-GVHD (p=0.0001). The OS of those patients with C-GVHD de novo (47m) and quiescent (44.8m) were superior than the OS of patients without C-GVHD (33.8%) or with the progressive form of C-GVHD (20.8m), p=0.002. The same effect was observed for the DFS in the de novo form (42.6m) and quiescent form (41.4m) of C-GVHD, with a DFS twice superior than the progressive form (19.8m) and than the C-GVHD absent (22.6m), p=0.001. When compared with cases without C-GVHD, the clinical severity of the C-GVHD (limited or extensive) showed a strong correlation with a higher DFS. Patients with limited C-GVHD had a DFS of 38.3m and the extensive form a DFS of 38.9m, significantly superior than the DFS of patients without C-GVHD with a DFS of 22.6m (p=0.002). Hence, this study shows the existence of a correlation between the presence of C-GVHD and higher OS and DFS in patients with haematological disorders submitted to allo-HCT. The diagnosis of progressive C-GVHD was associated to a deleterious effect over the outcome of allo-HCT, therefore inactivating the benefits of the graft versus tumour effect observed in the clinical presentations de novo and quiescent of C-GVHD.

scholarly journals Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 849-855 ◽  
Author(s):  
A von Bueltzingsloewen ◽  
R Belanger ◽  
C Perreault ◽  
Y Bonny ◽  
DC Roy ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Low Risk ◽  
Free Survival ◽  
Graft Versus Host ◽  
Disease Free ◽  
Acute Graft

The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low- risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

scholarly journals Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 849-855
Author(s):  
A von Bueltzingsloewen ◽  
R Belanger ◽  
C Perreault ◽  
Y Bonny ◽  
DC Roy ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Low Risk ◽  
Free Survival ◽  
Graft Versus Host ◽  
Disease Free ◽  
Acute Graft

Abstract The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low- risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

scholarly journals Improved graft-versus-host disease-free, relapse-free survival associated with bone marrow as the stem cell source in adults

Haematologica ◽  
2016 ◽  
Vol 101 (6) ◽  
pp. 764-772 ◽  
Author(s):  
R. S. Mehta ◽  
R. P. de Latour ◽  
T. E. DeFor ◽  
M. Robin ◽  
A. Lazaryan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Cell Source ◽  
Disease Free

scholarly journals Improved Graft-Versus-Host Disease-Free, Relapse-Free Survival (GRFS) Associated with Bone Marrow as the Stem Cell Source in Adults

2016 ◽  
Vol 22 (3) ◽  
pp. S49
Author(s):  
Rohtesh S. Mehta ◽  
Regis Peffault deLatour ◽  
Todd E. Defor ◽  
Marie Robin ◽  
Aleksandr Lazaryan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Cell Source ◽  
Disease Free

One Antigen HLA-Mismatched Related and 8/8 Allele Matched Unrelated Donors Are Associated with Similar Survival after Hematopoietic Cell Transplantation for Acute Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 965-965
Author(s):  
David Valcarcel ◽  
Fangyu Kan ◽  
Tao Wang ◽  
Stephanie J. Lee ◽  
Stephen R Spellman ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Related Donor ◽  
Disease Free

Abstract Patients in need of an allogenetic hematopoietic cell transplant but who lack an HLA genotypically identical sibling donor, are faced with the decision to consider a single HLA antigen mismatched related donor, or a search for a suitable 8/8 matched unrelated donor. We compared the outcomes of adult patients (≥18 years old) receiving a transplant for the treatment of AML or ALL in first or second remission from either a one-antigen mismatched related donor (MMRD group, N=89) reported to the CIBMTR or an 8/8 HLA-A, B, C and DRB1 allele matched unrelated donor (UD group, N=700) facilitated by the NMDP between 1995–2005. MMRD group was typed by serological or DNA-based methods for HLA-A, -B and –DR with all results verified by lab report review. The UD group was retrospectively typed for HLA-A, B, C and DRB1 by high resolution typing methods. Most received myeloablative conditioning regimens (77%), calcineurin inhibitor-based GVHD prophylaxis (100%) and T cell replete grafts (100%). 13% received ATG with the conditioning regimen. Median follow-up was 54 and 38 months in the MMRD and UD groups, respectively. The MMRD group was younger (median age 35 vs 43, p=0.002), had more ALL patients with low-risk cytogenetics (43% vs 18%, p=0.005), had older donors (median age: 38 vs 34, p=0.047), were more likely to receive methotrexate for GVHD prophylaxis (89% vs 77%, p=0.014) and were more likely to be transplanted prior to 2001 (62% vs 24%; p<0.001). There were no differences in patient or donor gender, diagnosis, disease-status, cytogenetic-risk of AML, time from diagnosis to transplant, stem cell source, conditioning regimen, use of ATG and Karnofsky index. Univariate comparisons (MMRD vs. UD) showed: 3-year OS (42% vs 44%, p=0.647), 3-year DFS (41% vs 41%, p=0.931), 3-year TRM (39% vs 31%, p=0.136), 3-year incidence of relapse (20% vs 28%, p=0.094), grade III–IV acute GVHD by 100 days (22% vs. 15%, p=0.147), chronic GVHD by 1 year (35% vs 47%, p=0.029). All multivariate analyses were adjusted for patient and transplant characteristics and are shown in the table below. In summary, transplants utilizing one-antigen mismatched related and 8/8 allele-matched unrelated donors did not significantly differ in overall survival or disease free survival, but chronic GVHD was more frequent after UD transplantation. Outcome RR (MMRD vs. UD) 95% CI p-value Survival 0.99 0.73–1.34 0.94 Disease-free survival 1.06 0.80–1.41 0.69 Treatment related mortality 1.14 0.77–1.69 0.52 Relapse 0.81 0.50–1.30 0.38 Acute GVHD III–IV 1.53 0.91–2.57 0.11 Chronic GVHD 0.58 0.39–0.85 0.006

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