Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1572-1579 ◽  
Author(s):  
Franco Locatelli ◽  
Marco Zecca ◽  
Roberto Rondelli ◽  
Federico Bonetti ◽  
Giorgio Dini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Graft Versus Host Disease ◽  
Cyclosporine A ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Leukemia Relapse

Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P = .06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs-A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P = .034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P = .15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect.

Reduction in the Incidence and Severity of Graft Versus Host Disease in HLA-Matched and Haploidentical Bone Marrow Transplantation Using Posttrasplant Cyclophosphamide. Experience of Two Latino-American Institutions

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5880-5880
Author(s):  
Roberto Ovilla ◽  
Uendy Perez-Lozano ◽  
Dannia Calles-Payan ◽  
Lucia A Reynolds-Ocampo ◽  
Gabriela Ruiz-Reyes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
High Dose ◽  
Host Disease ◽  
Graft Versus Host

Abstract The Graft Versus Host Disease (GVHD) grades II-IV is present in up to 40% in Human Leucocyte Antigen (HLA) - identical related transplants and up to 80% of non-related. The HLA-haploidentical bone marrow transplantation (BMT) has been associated with significant risks of graft rejection and severe GVHD, as an excessive alloreactivity by host and donor T cells. High dose of Cyclofosfamide (Cy) after BMT inhibits both graft rejection and GVHD. We want to share our experience in preventing GVHD in HLA - haploidentical alloBMT and HLA-matched related BMT using the strategy of Cy post-Transplant. We evaluated 25 patients from March 2013 to June 2014, all of them were in advanced stages of the disease or they have characteristics of poor prognosis before transplantation. All patients received non-myeloablative conditioning and Cyclofosfamide (Cy) 50 mg/Kg postrasplant (on days 3 and 4 after transplantation), Mycophenolate mofetil (from day 5 to 35) and Tacrolimus (from day 5 to 180). The 64% (16) were male, mean age 30.6 years (range 2 – 67 years), with a average follow-up of 198 days (range 14-512 days). The 76% (19) were HLA-matched related alloBMT (7 patients) and HLA-haploidentical alloBMT (12 patients) in hematological malignancies, the rest of trasplants (24%) were HLA-haploidentical alloBMT in benign hematological diseases, overall survival (OS) at day 180 by type of transplant was 70%, 64%, and 67% respectively. 28% (7) had graft failure. 11 patients had no acute GVHD, 10 patients had GVHD grade I-II, and 3 patients had grade III, only 1 patient died because of grade IV (P = 0.005). Chronic GVHD occurred in 4 patients (16%). As a complication related to Cy therapy, hemorrhagic cystitis was observed 32%(8). Posttransplantation cyclophosphamide is able to reduce the likelihood of developing chronic GVHD and reduces the severity of acute GVHD, it plays an important role in the feasibility of a haploidentical transplant because the lower incidence of GVHD. Our results showed one of the most satisfactory and encouraging studies on the use of post-transplantation Cy performed in Latin America. Disclosures No relevant conflicts of interest to declare.

Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2391-2398
Author(s):  
Tapani Ruutu ◽  
Liisa Volin ◽  
Terttu Parkkali ◽  
Eeva Juvonen ◽  
Erkki Elonen
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Study Groups ◽  
Host Disease ◽  
Graft Versus Host ◽  
Sibling Donor ◽  
To Receive

The role of corticosteroids in the prophylaxis of graft-versus-host disease (GVHD) is not well established. We have conducted a prospective, randomized, open-label, single-center study about the effect of adding methylprednisolone (MP) to the widely used prophylactic regimen consisting of cyclosporine A and methotrexate. A total of 108 consecutive patients treated with allogeneic bone marrow transplantation from an HLA-identical sibling donor for malignant blood disease were entered into the study; 53 patients were randomized to receive and 55 were randomized not to receive prophylactic MP. The dose of MP was 0.5 mg/kg on days 14 to 20, 1 mg/kg on days 21 to 34, 0.5 mg/kg on days 35 to 48, and thereafter the dose was slowly tapered and the administration discontinued on day 110. In the group given prophylactic MP, the incidence of acute GVHD was lower (19% vs 56%,P = .0001), there was a trend toward a lower incidence of chronic GVHD among low-risk patients (P = .06), and during the first 4 months the time spent at hospital was shorter and there were fewer infections. The total amount of MP given was similar in the study groups because of a higher incidence of acute GVHD and its treatment in the group of patients not given prophylactic MP. There were no significant differences between the study groups in relapse rate or survival. In conclusion, the addition of MP to the combination of cyclosporine and methotrexate markedly reduced the incidence of acute GVHD without causing untoward effects. The timing of corticosteroid administration is probably important for the efficacy.

scholarly journals Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2459-2464 ◽  
Author(s):  
K Atkinson ◽  
MM Horowitz ◽  
RP Gale ◽  
DW van Bekkum ◽  
E Gluckman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Risk Factor ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host

Abstract Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.

scholarly journals Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2459-2464 ◽  
Author(s):  
K Atkinson ◽  
MM Horowitz ◽  
RP Gale ◽  
DW van Bekkum ◽  
E Gluckman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Risk Factor ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.

Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2391-2398 ◽  
Author(s):  
Tapani Ruutu ◽  
Liisa Volin ◽  
Terttu Parkkali ◽  
Eeva Juvonen ◽  
Erkki Elonen
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Study Groups ◽  
Host Disease ◽  
Graft Versus Host ◽  
Sibling Donor ◽  
To Receive

Abstract The role of corticosteroids in the prophylaxis of graft-versus-host disease (GVHD) is not well established. We have conducted a prospective, randomized, open-label, single-center study about the effect of adding methylprednisolone (MP) to the widely used prophylactic regimen consisting of cyclosporine A and methotrexate. A total of 108 consecutive patients treated with allogeneic bone marrow transplantation from an HLA-identical sibling donor for malignant blood disease were entered into the study; 53 patients were randomized to receive and 55 were randomized not to receive prophylactic MP. The dose of MP was 0.5 mg/kg on days 14 to 20, 1 mg/kg on days 21 to 34, 0.5 mg/kg on days 35 to 48, and thereafter the dose was slowly tapered and the administration discontinued on day 110. In the group given prophylactic MP, the incidence of acute GVHD was lower (19% vs 56%,P = .0001), there was a trend toward a lower incidence of chronic GVHD among low-risk patients (P = .06), and during the first 4 months the time spent at hospital was shorter and there were fewer infections. The total amount of MP given was similar in the study groups because of a higher incidence of acute GVHD and its treatment in the group of patients not given prophylactic MP. There were no significant differences between the study groups in relapse rate or survival. In conclusion, the addition of MP to the combination of cyclosporine and methotrexate markedly reduced the incidence of acute GVHD without causing untoward effects. The timing of corticosteroid administration is probably important for the efficacy.

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