scholarly journals Differences in Graft-versus-Host Disease Characteristics between Haploidentical Transplantation Using Post-Transplantation Cyclophosphamide and Matched Unrelated Donor Transplantation Using Calcineurin Inhibitors

2020 ◽  
Vol 26 (11) ◽  
pp. 2082-2088
Author(s):  
Melhem M. Solh ◽  
Jimena Baron ◽  
Xu Zhang ◽  
Asad Bashey ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Calcineurin Inhibitors ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Post Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Haploidentical Transplantation ◽  
Disease Characteristics

Tacrolimus Versus Cyclosporine for Graft-Versus-Host Disease Prophylaxis in Pediatric Patients Undergoing Matched Unrelated Donor Hematopoietic Stem Cell Transplants. A Pediatric Blood and Marrow Transplant Consortium Study..

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2883-2883 ◽  
Author(s):  
Mark P. Atlas ◽  
Gregory Yanik ◽  
Rakesh Goyal
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Calcineurin inhibitors form the backbone of graft versus host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation. In the adult literature tacrolimus was demonstrated superior to cyclosporine in preventing grade II–IV acute GVHD in both related and unrelated donor transplants; however, there is no data comparing their efficacy in the pediatric population. In a multi-institutional trial, we prospectively evaluated the clinical data on 102 patients receiving either cyclosporine/methotrexate or tacrolimus/methotrexate based prophylactic regimens for 6/6 matched unrelated donor, transplant. Conditioning regimens were fully ablative; no T-cell depletion was permitted; cord blood donors were excluded. Patients were required to receive either cyclosporine or tacrolimus, but the choice was per investigator preference. The two arms were reasonably balanced: 59.8% of patients received cyclosporine and 40.2% of patients received tacrolimus. Rates for maximum grade II–IV acute GVHD were 37.7% for cyclosporine and 39% for tacrolimus (p = 0.89). Rates for maximum grade III–IV acute GVHD were 19.6% for cyclosporine and 24.4% for tacrolimus (p = 0.57). Incidence of chronic GVHD in 97 evaluable patients was 37.9% in 58 patients who received cyclosporine and 35.8% in 39 patients who received tacrolimus (p = 0.84). Survival at 1 year post-transplant was similar in both groups: 59.2% for cyclosporine and 51.2% for tacrolimus (p= 0.31). Toxicity analysis is ongoing. In pediatric matched unrelated donor transplantation, the efficacy of tacrolimus/methotrexate and cyclosporine/methotrexate based regimens for prophylaxis of GVHD are not significantly different.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Abstract Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

Outcome of Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia: Comparison of Matched Related Donor Verses Matched Unrelated Donor. Important Role of Graft Versus Host Disease in Preventing Relapse.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5153-5153
Author(s):  
Adam Gassas ◽  
Lillian Sung ◽  
Prabodh Das ◽  
Jonanne K. Hitzler ◽  
Ronald Grant ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Low Grade ◽  
High Grade ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Remission Status ◽  
Related Donor

Abstract Seventy percent of children with acute lymphoblastic leukemia (ALL) who benefit from stem cell transplantation (SCT) lack a human leukocyte antigen (HLA) matched related donor (MRD). For these children SCT from a matched unrelated donor (MUD) represents an alternative therapeutic option. Our objective was, to review the outcome of children (0–18years) with ALL whom received a fully matched marrow allografts at our institution between July 1998 - December 2003. All children were conditioned with cyclophosphamide (50mg/kg infused over 1 hour daily for 4 days) followed by fractionated total body irradiation (TBI; 1200cGy, 6 fractions over 3 days). Cyclosporine A and a short course of methotrexate were used for graft versus host disease (GVHD) prophylaxis. Results: We performed 23 fully MRD and 23 fully MUD SCT during the study period. Median age at time of SCT was 10.2 y (range 2.2–17.5) and 8.2 y (range 1–16.5) for the MRD and MUD groups, respectively. Remission status at time of SCT; For the MRD group, complete remission (CR) 1, 2 and 3 were 5, 15 and 3 patients, respectively. For the MUD group, CR 1, 2 and 3 were 6, 14 and 3 patients, respectively. All patients engrafted for neutrophils (defined as absolute neutrophil count (ANC) of > 0.5 x 109/l for 2 consecutive days) with a median time of 18 days (range 12–28) and 16 days (range 10–25) for the MRD and MUD groups, respectively. In both groups, low grade acute(a) GVHD (I-II) occurred in 50% of the cases. However, high grade aGVHD (III-IV) occurred in 7/23 patients in the MUD group compared to only 1 patient with grade III aGVHD in the MRD group. Three years event free survival (EFS) for the whole group was 47 ± 8% with overall survival (OS), 50 ± 8%. EFS (3y) according to remission status was; 64 ± 15% for CR1, 51 ± 10% for CR2 and 33 ± 19% for CR3, P = 0.06. Twelve out of thirteen deaths in the MRD group were caused by leukemia relapse versus 3 out of 8 deaths in the MUD group. Transplant related mortality (TRM) was 5/8 deaths in the MUD group versus 1/13 deaths in the MRD group. Three years EFS and overall survival (OS) were, 37 ± 11%, 39 ± 11% for the MRD group and 63 ± 10%, 64 ± 10% (P = 0.16) for the MUD group. For the whole group, EFS according to aGVHD was, 29 ± 15% for no aGVHD, 51 ± 11% for low grade aGVHD and 60 ± 15% for high grade. Conclusion: Acute graft versus host disease is associated with less relapse post SCT for pediatric ALL, presumably through a graft-versus-leukemia effect. Our data suggests that outcomes can be improved further through exploring means of inducing aGVHD while reducing the toxicity of SCT. In MRD SCT where the likelihood of aGVHD is less and therefore relapse rate is higher, and in order to maximize survival in the non aGVHD group, attempts for aGVHD induction by early manipulation of the immunosuppressive medications or a low dose pre-emptive donor lymphocyte infusion in the first 60 days post engraftment, need to be explored in future studies.

Chronic Graft-Versus-Host Disease after Tacrolimus Versus Cyclosporine for Graft-Versus-Host Disease Prophylaxis in Pediatric Patients Undergoing Matched Unrelated Donor Hematopoietic Stem Cell Transplantation. A Pediatric Blood and Marrow Transplant Consortium Study..

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4984-4984
Author(s):  
Mark P. Atlas ◽  
Greg Yanik ◽  
Kirk R. Schultz ◽  
Rakesh K. Goyal
Keyword(s):  
Hematopoietic Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Chronic graft versus host disease (GVHD) is a significant cause of morbidity and mortality in matched unrelated donor hematopoietic stem cell transplantation. Incidence of acute GVHD is a major risk factor for chronic GVHD. Calcineurin inhibitors form the backbone of graft versus host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation. When comparing cyclosporine to tacrolimus for GVHD prophylaxis, we previously reported a trend toward superiority of cyclosporine as prophylaxis against acute GVHD. We now analyze their effect on the incidence and severity of chronic GVHD. In a multi-institutional trial, we prospectively collected the clinical data on 141 evaluable patients receiving either cyclosporine/methotrexate or tacrolimus/methotrexate based prophylactic regimens for 6/6 matched unrelated donor, transplant. Conditioning regimens were fully ablative; no T-cell depletion was permitted; cord blood donors were excluded. Patients were required to receive either cyclosporine or tacrolimus, but the choice was per investigator preference. The two arms were reasonably balanced: 60.1% of patients received cyclosporine and 39.9% of patients received tacrolimus. Rates for acute GVHD were 60.4% for cyclosporine and 73.8% for tacrolimus (p = 0.086). Rates for chronic GVHD were 44.2% for cyclosporine and 47.3% for tacrolimus (p = 0.7). In the 61 patients with chronic GVHD, extensive disease was present in 82.9% of cyclosporine group and 80.8% of the tacrolimus group (p = 1.0) Those graded as moderate or severe comprised 80% of the cyclosporine group and 56% of the tacrolimus group (p = 0.46) and those both extensive and moderate or severe were 71.4% and 52%, respectively (p = 0.12). In pediatric matched unrelated donor transplantation, the incidence and severity of chronic graft versus host disease in patients receiving either tacrolimus/methotrexate or cyclosporine/methotrexate based regimens for prophylaxis of GVHD are not significantly different.

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