Risk Factors for Graft-versus-Host Disease (GVHD) Following Myeloablative HLA-Identical Sibling Transplantation with Allogeneic Peripheral Blood Stem Cells (PBSC): An Analysis of 546 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3318-3318
Author(s):  
Mohamad Mohty ◽  
Keyword(s):  
Risk Factors ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Individual Patient Data ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Factors Associated ◽  
Disease Free

G-CSF-mobilized PBSCs are increasingly used in allogeneic transplantation. In comparison to bone marrow (BM), PBSCs have been shown to allow faster engraftment, but also can lead to more chronic GVHD. Our current knowledge of risk factors for GVHD is based primarily on historical analyses performed using BM as the stem cell source. This analysis sought to identify potential risk factors predicting for the development of acute and chronic GVHD after related HLA-identical PBSC transplantation (PBSCT). We analyzed the outcome of 546 patients who were part of an international database bringing together individual-patient data from nine randomized trials. Median age of recipients was 39 years. 180 (33%) patients had acute myeloid leukemia (AML), 237 (43%) had chronic myeloid leukemia (CML) and 129 patients had other hematological malignancies. 398 (73%) patients had standard risk disease at time of PBSCT and 218 (41%) patients received TBI-based myeloablative conditioning. 312 (57%) patients received short-course methotrexate (days 1, 3, 6) as GVHD prophylaxis, while 234 (43%) received long-course methotrexate (days 1, 3, 6, 11). 190 (35%) patients received G-CSF post-transplant. An ANC of >500/μL was reached at a median of 16 (range, 8–50) days. Platelet recovery occurred at a median of 15 (range, 5–376) days. The incidence of grades II-IV acute GVHD was 44% (95%CI, 40–48%), while the incidence of extensive chronic GVHD was 40% (95%CI, 36%–44%). In a Cox multivariate analysis, the incidence of acute GVHD was significantly associated with age (P=0.001; RR=1.60 for age >40; 95%CI, 1.2–2.1), and TBI-based conditioning (P=0.0009; RR=1.7; 95%CI, 1.2–2.2). The main risk factors associated with an increased risk of extensive chronic GVHD in a Cox multivariate analysis were grade II-IV acute GVHD and a female donor (P=0.009; RR=1.5; 95%CI, 1.1–2.0; and P<0.0001; RR=2.2; 95%CI, 1.6–2.9 respectively). At a median follow-up of 35 months, disease-free survival (DFS) was significantly higher in patients with extensive chronic GVHD compared to patients without extensive chronic GVHD (P=0.03). G-CSF post-transplant (P=0.0027; RR=1.9; 95%CI, 1.2–2.9), disease status at transplant ((P<0.0001; RR=2.9 for advanced diseases; 95%CI, 1.9–4.3), and a diagnosis of acute leukemia (AML or ALL; P<0.0001; RR=3.5; 95%CI, 2.2–5.6) were the major factors associated with worsened disease-free-survival. In conclusion, although the use of PBSCs is associated with more frequent and clinically more severe chronic GVHD, this large-scale analysis based on individual-patient data demonstrates that some risk factors for GVHD after PBSCT are qualitatively comparable to those observed with BM-derived stem cells and might be determinant for the ultimate outcome. Most importantly, extensive chronic GVHD is associated with significantly improved DFS, while the use of G-CSF post-transplant might be detrimental.

Hematopoietic Stem Cell Transplantation after Reduced Intensity Conditioning in Acute Myeloid Leukemia Patients Older Than 40 Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5074-5074
Author(s):  
Cynthia Huisman ◽  
Ellen Meijer ◽  
Eefke J. Petersen ◽  
Henk M. Lokhorst ◽  
Leo F. Verdonck
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

Abstract Reduced intensity conditioning (RIC) protocols are increasingly used for allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients. We retrospectively analyzed the outcome of RIC HSCT in a homogeneous group of acute myeloid leukemia (AML) patients over the age of 40. Forty-three AML or high-risk myelodysplastic syndrome patients were treated with a fludarabine and low dose total body irradiation (TBI) based regimen, followed by a full peripheral stem cell graft. Antithymocyte globulin was given to matched unrelated recipients (34%) before infusion of fludarabine. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin and mycophenolate mofetil. All but 2 AML patients were in complete remission at the time of transplantation. Seventy-six percent of patients had a poor risk profile. Hematologic recovery was fast and primary graft failure occurred in one patient. Two patients with active disease at the time of HSCT experienced ongoing relapse. Infections were diagnosed in 9 patients (21%) and 6 patients (14%) were treated for CMV reactivation. Sixty percent of patients developed acute GVHD, which was grade 2 in 40% and grade 3 in 12%. Chronic GVHD occurred in 33% of patients. The incidence and severity of both acute and chronic GVHD was similar in patients with related and unrelated donors (P = 0.84 and 0.74, respectively). Treatment-related mortality (TRM) was low (9%), total nonrelapse mortality was 19%. After a median follow-up of 571 days, 16 patients (37%) experienced relapse. One-year progression-free and overall survival were 61% and 67%, respectively. Median disease-free survival has not been reached yet (> 58 months) and median overall survival was 31 months (Fig 1 and 2, respectively). Poor risk AML was significantly associated with disease-free survival in multivariate analysis (P = 0.02). Age > 60 years, gender, donor type, timing of RIC HSCT (upfront or after relapse) and acute GVHD were not identified as prognostic factors. In conclusion, fludarabine plus low-dose TBI-based RIC HSCT is effective in AML patients over the age of 40 without active disease at the time of transplant and is associated with low TRM. Figure Figure Figure Figure

HLA DR15 Antigen Status Does Not Impact Graft-Versus-Host Disease or Disease-Free Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3094-3094
Author(s):  
Minoo Battiwalla ◽  
Kristin Ellis ◽  
Steven Z. Pavletic ◽  
Gorgun Akpek ◽  
Peiman Hematti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Matched Sibling ◽  
Disease Free

Abstract Abstract 3094 The HLA class II DRB1 antigen DR15 is an important immunobiologic marker in immune mediated marrow failure states. DR15 has also been reported in small studies to be associated with favorable outcomes (reduction in acute GVHD and reduced relapse resulting in improved overall survival) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on major transplant outcomes, we conducted a retrospective study of 2, 891 recipients of first marrow or mobilized peripheral blood stem cell transplantation for the treatment of acute myeloid leukemia (n=1038), acute lymphoblastic leukemia (n=700), chronic myeloid leukemia (n=948), or myelodysplastic syndrome (n=205) between 1990–2008 and reported to the CIBMTR registry. Selection was confined to HLA-identical sibling transplantation to avoid HLA-disparity as a driving force for observed differences. All patients received conventional myeloablative conditioning, T-replete grafts and cyclosporine plus methotrexate- based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 (25.3%) patients as positive and 2159 (74.7%) patients as negative for DRB1*15 :01 or *15 :02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15-positive and -negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, acute graft-versus-host disease (GvHD) II-IV or III-IV, chronic GVHD, treatment related mortality, relapse, disease-free survival or overall survival. Confining the univariate analysis to myeloid malignancies did not alter these findings. Multivariate analysis models were constructed with DR15 status forced into the models in all steps of model building and the final model regardless of its statistical significance. Other variables tested included: donor/recipient age, CMV status, disease, disease stage, graft source, Karnofsky score, race and year of transplant. Variables that attained a p-value ≤0.05 were held in the final multivariate models. In multivariate analysis, DR15 status showed no significant difference in the primary outcomes of acute GVHD II-IV or III-IV, chronic GVHD, overall survival, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplantation outcomes in this large and homogenous cohort of leukemia and MDS patients. Disclosures: No relevant conflicts of interest to declare.

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

scholarly journals Allogeneic Peripheral Blood Stem-Cell Compared With Bone Marrow Transplantation in the Management of Hematologic Malignancies: An Individual Patient Data Meta-Analysis of Nine Randomized Trials

2005 ◽  
Vol 23 (22) ◽  
pp. 5074-5087 ◽  
Keyword(s):  
Late Stage ◽  
Randomized Trials ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Stage Disease ◽  
Disease Free

Purpose Considerable uncertainty exists regarding relative effects of allogeneic peripheral blood stem cells transplantation (PBSCT) versus bone marrow transplantation (BMT) on outcomes of patients with hematologic malignancies. Patients and Methods To provide the totality of research evidence related to the effects of PBSCT versus BMT, we conducted an individual-patient data meta-analysis using data from nine randomized trials enrolling 1,111 adult patients. Results Compared with BMT, PBSCT led to faster neutrophil (odds ratio [OR] = 0.31; 95% CI, 0.25 to 0.38; P < .00001) and platelet engraftment (OR = 0.52; 95% CI, 0.44 to 0.61; P < .00001). PBSCT was associated with a significant increase in the development of grade 3-4 acute graft-versus-host disease (GVHD; OR = 1.39; 95% CI, 1.03 to 1.88) and extensive (47% v 31% at 3 years; OR = 1.89; 95% CI, 1.47 to 2.42; P < .000001) and overall chronic GVHD (68% v 52% at 3 years; OR = 1.92; 95% CI, 1.47 to 2.49; P < .000001), but not grade 2-4 acute GVHD (54% v 53%; P = .49). PBSCT was associated with a decrease in relapse (21% v 27% at 3 years; OR = 0.71; 95% CI, 0.54 to 0.93; P = .01) in both late-stage–(33% v 51% at 3 years; OR = 0.59; 95% CI, 0.38 to 0.93; P = .02) and early-stage–disease patients (16% v 20% at 3 years; OR = 0.69; 95% CI, 0.49 to 0.98; P = .04). Nonrelapse mortality was not different between groups. Overall and disease-free survival were only statistically significantly improved in patients with late-stage disease (overall survival: 46% v 31% at 3 years; OR = 0.64; 95% CI, 0.46 to 0.90; P = .01; disease-free survival: 41% v 27% at 3 years; OR = 0.63 95% CI, 0.45 to 0.87; P = .01). Conclusion PBSCT is associated with a decreased relapse rate in hematologic malignancies and improvement in overall and disease-free survival in patients with late-stage disease. PBSCT is also associated with a significant risk of extensive chronic GVHD.

Analysis of 120 Pediatric Patients with Non-Malignant Disorders Transplanted Using Unrelated Plasma Depleted Cord Blood and the Role of Post-Thaw Wash

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4406-4406
Author(s):  
Joseph Rosenthal ◽  
Tang-Her Jaing ◽  
Lee Lee Chan ◽  
Gretchen Eames ◽  
Michael L. Graham ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Pediatric Patients ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Unrelated cord blood (UCB) is an important stem cell source for unrelated hematopoietic cell transplantation of patients with non-malignant disorders. Cell dosage is a critical factor for successful UCB hematopoietic stem cell transplantation (HSCT). The red cell reduced (RCR) and post-thaw wash techniques that are widely used incur significant nucleated cell loss. Three strategies were employed to maximize cell dose and improve outcome–use of cord blood processed with plasma depletion without red blood cell reduction (PD CB), avoidance of post-thaw wash, and the use of double cords (2X) when necessary. A CIBMTR-audited analysis was performed on all 120 pediatric patients with non-malignant disorders transplanted with PD CB at 29 U.S. and 17 international centers. Transplant characteristics: median age 3.5 years (range 0.1–14); median patient weight 15 kg (range 4–61); male 58%. The majority of patients (n=58; 55%) were Asian. Twenty-two (21%) patients were Hispanic, 15 (14%) were Caucasian, 6 (6%) were African-American, and three (3%) were of Middle Eastern background. HLA ABDR matches: 6/6–26; 5/6–48; 4/6–47; 3/6 or 2/6–6; median pre-freeze nucleated cell dose 10.5×107/kg; median pre-freeze CD34+ dose 3.7×105/kg; non-myeloablative regimen 24%; 58% infused without post-thaw wash (NW). Myeloid engraftment defined as ANC≥500 and 6-month platelet engraftment defined as ≥ 20K and ≥ 50K are 89±8%, 88±8%, and 84±6% respectively. The median time to myeloid and platelet engraftment are 21 days (range 11–64), 49 days (range 13–155), and 61.5 days (range 21–205) respectively. No major adverse event was observed in either the W or the NW group. The cumulative incidence of reported grade II–IV acute GVHD was 38±5%, and 19±4% had grade III–IV acute GVHD. 36±6% developed limited chronic GVHD, and 12±4% developed extensive chronic GVHD. With a median follow-up of 329 days (range 3–1928 days), the Kaplan-Meier estimates of 1-year TRM, OS and diseasefree survival were 20±6%, 88±6% and 72±6% respectively. Foregoing post-thaw wash for PD CB transplantation improved neutrophil (RR=1.75; p=0.01) and platelet engraftment (RR=1.72; p=0.02) and reduced TRM (RR=0.38; p=0.04). This series demonstrated that unrelated PD CB transplantation can be performed safely and effectively in children with life-threatening, non-malignant disorders. Additionally, the results demonstrate possible improvement in myeloid and platelet engraftment, overall and disease-free survival when post-thaw wash is not employed. Table 1. Summary of overall results Outcome All Patients N = 120 Washed CB N = 48 Unwashed CB N = 71 RR (Wash=Ref) P-value ANC500 Engraftment Cumulative Incidence Median # Days to Engraftment 87±6% d+21 86±9% d+25 89±8% d+19 1.75 0.01 Platelet 20K Engraftment Cumulative Incidence Median # Days to Engraftment 81±6% d+49 75±9% d+52 88±9% d+43 1.72 0.02 Autologous Recovery 3±2% 2±2% 4±3% 1.06 0.95 Acute GvHD II–IV Acute GvHD III–IV 38±5% 19±4% 31±7% 17±6% 45±7% 21±6% 1.74 1.38 0.11 0.50 Chronic GvHD Limited Chronic GvHD Extensive 36±6% 12±4% 14±6% 19±6% 60±10% 6±4% 5.69 0.24 &lt;0.001 0.08 Transplant-Related Mortality–100 Day Transplant-Related Mortality–3 Yr 10±3% 20±4% 11±5% 34±8% 9±4% 11±4% 0.38 0.04 Overall Survival–1 Yr Overall Survival–3 Yr 79±4% 79±4% 66±8% 66±8% 88±4% 88±4% 0.43 0.06 Disease-Free Survival–1 Yr Disease-Free Survival–3 Yr 72±5% 70±6% 58±9% 51±10% 84±5% 84±5% 0.48 0.07

scholarly journals Unrelated donor marrow transplantation in children

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3247-3256 ◽  
Author(s):  
A Balduzzi ◽  
T Gooley ◽  
C Anasetti ◽  
JE Sanders ◽  
PJ Martin ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Karnofsky Score ◽  
Obstructive Pulmonary Disease ◽  
Free Survival ◽  
Disease Free

Abstract Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA- mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Unrelated donor marrow transplantation in children

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3247-3256 ◽  
Author(s):  
A Balduzzi ◽  
T Gooley ◽  
C Anasetti ◽  
JE Sanders ◽  
PJ Martin ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Karnofsky Score ◽  
Obstructive Pulmonary Disease ◽  
Free Survival ◽  
Disease Free

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA- mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Comparable 3-Year Disease-Free Survival Regardless of Anti-Thymocyte Globulin Inclusion in Pediatric Myeloablative Cord Blood Transplantation for Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1259-1259
Author(s):  
Doris M. Ponce ◽  
Rodney Sparapani ◽  
Junfang Chen ◽  
Vanderson Rocha ◽  
Daniel H. Fowler ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Acute Gvhd ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Disease Status ◽  
Free Survival ◽  
Grade Ii ◽  
Disease Free ◽  
Grade Iii

Abstract Background: Cord blood (CB) is routinely used as an alternative stem cell source for the treatment of children with acute leukemia and has been associated with high rates of disease-free survival (DFS). However, one controversial issue in pediatric CB transplantation is the role of anti-thymocyte globulin (ATG) as immunoprophylaxis. While inclusion of ATG in the conditioning may decrease the risk of graft-versus-host disease (GVHD), it could potentially abrogate graft-versus-leukemia effects and increase the risk of opportunistic infections. Thus, we compared outcomes in a uniform group of pediatric patients with acute lymphoblastic leukemia (ALL) who underwent myeloablative CB transplantation with or without ATG. Methods: Patients with ALL in morphologic remission (CR1 n=106, CR2 n=146, CR3 n=45) aged ≤ 20 years transplanted between 01/2007-12/2011 with high-dose total body irradiation-based conditioning and single or double unit CB grafts were eligible for analysis. CB units were 4-6/6 HLA-A,-B at the antigen-level, -DRB1 allele matched to the recipient and had CB unit with cryopreserved total nucleated cell dose of ≥ 2.5 x107/kg/unit. Cox regression models were built to evaluate potential differences in outcome in ATG versus non-ATG CB transplant recipients. The primary endpoint was 3-year DFS. Results: Of 297 patients, 92 received ATG and 205 did not. Age and disease status were similar in each group whereas ATG recipients were less likely to be CMV seropositive and more likely to receive single unit CB grafts. While neutrophil engraftment was similar in each group, the risk of day 100 grade II-IV acute GVHD [30% (95%CI: 21-40) versus 54% (95%CI: 47-61), p = 0.0002] and 3-year chronic GVHD [22% (95% CI: 14-31) versus 43% (95% CI: 36-50), p = 0.0008] were decreased in ATG recipients. However, day 100 grade III-IV aGVHD was comparable: 11% (95%CI: 5-18) in ATG versus 17% (95%CI: 12-23) in non-ATG recipients, p = 0.15]. The 3-year TRM was similar in both groups: 16% (95%CI: 10-25) in ATG versus 17% (95%CI: 13-23) in non-ATG recipients (p = 0.98). Relapse was also similar in ATG and non-ATG recipients: 17% (95%CI: 10-23) versus 27% (95%CI: 21-34, p = 0.12), respectively. In multivariate analysis, negative CMV serostatus was associated with reduced TRM risk [HR 0.55 (95%CI: 0.30-0.98), p = 0.004] whereas remission status CR2 or CR3 significantly increased relapse risk [HR 2.18 (95%CI: 1.22-3.89), p = 0.008], but inclusion of ATG had no effect on either outcome. With a median follow-up of survivors of 36 months (range 5-72), the 3-year DFS was 66% (95%CI: 56-76) and 55% (95%CI: 48-62) in ATG and non-ATG recipients, respectively (p = 0.23, Figure 1). The distribution of causes of death was similar in each group. In multivariate analysis, treatment failure risk was increased in patients transplanted in CR2 or CR3, but the inclusion of ATG had no effect (p = 0.24) (Table 1). Conclusion: Inclusion of ATG in pediatric myeloablative CB transplant for ALL is associated with a decreased risk of grade II-IV acute GVHD and chronic GVHD but not severe grade III-IV acute GVHD. There was no difference in 3-year DFS in each group and multivariate analysis revealed ATG inclusion had no impact upon treatment failure risk. These results indicate that optimization of both ATG and non-ATG conditioning platforms are needed in order to further improve CB transplantation survival in children with ALL. Unanswered questions include the impact of the formulation, dose and timing of ATG administration. These findings cannot be extrapolated for other diagnoses, reduced intensity conditioning, or adults. Table 1 Hazard ratio(95% confidence interval) p-value ATG use Conditioning without ATG Conditioning with ATG 1.00 0.78 (0.52 – 1.18) 0.24 Disease status CR1 CR2, CR3 1.00 2.01 (1.31 – 3.08) 0.001 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Triple Post-Transplant Cyclophosphamide (PTCY) Based Gvhd Prophylaxis for HLA Matched or HLA Haploidentical Transplants

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4881-4881
Author(s):  
Eugenio Galli ◽  
Elisabetta Metafuni ◽  
Sabrina Giammarco ◽  
Maria Assunta Limongiello ◽  
Idanna Innocenti ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Age Over 60 ◽  
Disease Free ◽  
Related Mortality

Abstract We report a retrospective analysis of 198 consecutive allogeneic stem cell transplant (HSCT) recipients, who received post transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mofetile as g raft-versus-host-disease (GVHD) prophylaxis. The donor was either HLA matched (n=78) (siblings -32- or unrelated -46) , or a haploidentical relative (HAPLO) (n=120). End points of the study were acute and chronic GVHD, transplant related mortality (TRM), relapse, disease free survival (DFS) and graft versus host and relapse free survival (GRFS). The two groups were comparable except for an older age (49 vs 56 years) in the haplo-HLA group. The diagnosis was mainly acute leukemia (57%), myelofibrosis (21%) or lymphoma (12%). Conditioning was myeloablative in 77% and 73% respectively (p=0.57). Acute GVHD grade II-IV developed in 10% of the HLA matched transplants vs 27% in the HAPLO group (p=0.005). The latter also had more moderate-to-severe cGVHD (4% vs 23%, p&lt;0.001). The cumulative incidence of transplant related mortality (TRM) at 1 year for the HLA matched vs HAPLO patients, was 10% vs 21% (p=0.04) (Fig.1) , with age over 60 years being the major negative predictor in multivariate analysis. Relapse at 1 year was 24% for HLA matched vs 10% for HAPLO transplants (p=0.051) (Fig.1). Disease free survival (DFS) at 1 year was 65% and 68% in matched and HAPLO patients, respectively (p=0.85) (Fig.1) and GRFS 55% vs 49% (p=0.18). In multivariate analysis, age over 60 years was the strongest predictor of DFS and GRFS (HR 1.73, p=0.03 and HR 1,65, p= 0.02). In conclusion: when using the same triple PTCY based GVHD prophylaxis, HLA matched grafts are associated with significantly less acute and chronic GvHD, if compared with HAPLO grafts. There is a trend for reduced TRM at 1 year, especially in chronic myelo-lymphoproliferative disorders, and a trend for increased relapse, resulting in identical disease free survival. Figure 1 Figure 1. Disclosures Laurenti: Gilead: Honoraria; Roche: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

Allogeneic Stem Cell Transplantation In Chronic Myeloid Leukemia In TKIs Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5554-5554
Author(s):  
Parvez Ahmed ◽  
Syed Karman Mahmood ◽  
Tariq Mahmood Satti ◽  
Qamar Un Nisa Chaudhry ◽  
Nighat Shahbaz ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Treatment Option ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Standard Risk ◽  
Disease Free

Abstract Introduction Tyrosine kinase inhibitors (TKIs) have largely replaced allogeneic hematopoietic stem cell transplantation (HSCT) as first line treatment option in chronic phase chronic myeloid leukemia (CML) yet due to the need for continued administration the cost becomes prohibitive in majority of patients without any health insurance coverage. Therefore allogeneic stem cell transplant remains a reasonable treatment option for such patients especially in resource constrained countries. It is also useful treatment modality in children, CML in accelerated phase and in patients intolerant to TKIs. We report results of 64 consecutive patients undergoing HLA matched sibling allo HSCT at our center from April 2002 to September 2012. Methods Patients with Philadelphia positive CML were categorized into standard and high risk based on age >40 years, disease duration > 12 month from diagnosis to transplant and accelerated phase. Conditioning regimens used were oral busulphan 16 mg/kg plus cyclophosphamide 200 mg/kg (Bu16/Cy200), Bu16/Cy120, Bu16/Cy120/Etoposide30 and Bu16/Cy120/ATG. Source of stem cell was peripheral blood stem cells (PBSC) or bone marrow (BM) infusion. GVHD prophylaxis consisted of ciclosporin, short methotrexate (10 mg/m2 on day +1, 8 mg/m2 on day +3 & 6) ± prednisolone. Statistical calculations included Fisher’s exact test, Kaplan-Meier for survival analysis, and Cox regression for multivariate analysis. Results Median age of the patients was 28 years (range 7 – 54). Female donor to male recipient was seen in 12 cases while 20 patients had major blood group mismatch. Forty seven patients were standard risk while 17 were categorized as high risk. Bu16/Cy120 was the most common conditioning regimen given in 34 cases followed by Bu16/Cy200 in 19 cases. Fifty four patients received PBSC while BM was given in 8 cases. Grade I/II acute GVHD was seen in one-third of the cases while 7 (11%) had grade III/IV GVHD. Extensive chronic GVHD was seen in 10 (16%) cases while 12 (19%) patients had limited chronic GVHD. Complications observed were hemorrhagic cystitis (7), VOD (4), CMV infection (2) and septicemia (3). Five (8%) patients had disease relapse. The overall survival was 70.3% (median 1627 days) while disease free survival was 62.5% (median 1547 days). Nineteen patients died of various complications like extensive GVHD (n=5), septicemia (n=3), VOD (n=3), CMV infection (n=3) and disseminated aspergillosis (n==2). A significant difference was observed among patients bearing standard risk compared with those in high risk group in terms of overall survival (79% versus 47% , p=0.013), disease free survival (72% versus 35%, p=0.031) and incidence of acute GVHD (34% versus 71%, p=0.01) in univariate analysis. Age >40 year was the only factor associated with adverse outcome in multivariate Cox-regression model. Conclusions Early allogeneic HSCT in CML patients <40 years of age is associated with long term disease free survival in about 70% of cases. It is a reasonable treatment option in situations where TKIs cannot be employed as first line therapy due to various reasons. Disclosures: No relevant conflicts of interest to declare.

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