scholarly journals Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath

2001 ◽  
Vol 114 (3) ◽  
pp. 701-705 ◽  
Author(s):  
G. S. Vassiliou ◽  
D. K. H. Webb ◽  
D. Pamphilon ◽  
S. Knapper ◽  
P. A. Veys
Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5172-5172 ◽  
Author(s):  
Hiromasa Yabe ◽  
Shunichi Kato ◽  
Miharu Yabe ◽  
Kazuko Kudo ◽  
Hiroshi Yagasaki ◽  
...  

Abstract An optimum conditioning regimen is indispensable in improving outcomes for patients with acquired aplastic anemia (AA) who receive bone marrow transplantation (BMT) from an alternative donor. Although high-dose total body irradiation (TBI) is effective in enhancing engraftment, intensive conditioning regimens are associated with increased regimen-related toxicity, which results in a decreased success rate. Currently, two different approaches are primarily used; a conditioning regimen including low-dose TBI and a fludarabin-based regimen without TBI. We attempt to clarify the efficacy and regimen-related toxicity of these two approaches. Ten patients (7 males, 3 females; median age 12y; range 9–17y) underwent an alternative donor transplant following a conditioning regimen with low-dose TBI (TBI group); patients received cyclophosphamide (50 mg/kg/d on days −5 to −2), antithymocyte globulin (Thymoglobulin, 2.5 mg/kg/d on days −5 to −2) and TBI (2.5 Gy x 2 on day −1). The donor was unrelated in 9 patients (3 were serologically HLA A or B antigen mismatched; 3 were serologically HLA DR antigen mismatched, 1 was both serologically and genotypically DR antigen mismatched; 1 was genotypically DRB1 mismatched; 1 was a genotypically complete match) and was a family member in 1 patient (serologically HLA A-mismatched father). Twelve patients (6 males, 6 females; median age, 11 y; range 2–20 y) received a conditioning regimen of fludarabine (25 mg/kg/d on days −5 to −2), cyclophosphamide (750 mg/m 2 /d on days −5 to −2), thymoglobulin (1.5 mg/kg/d on days −5 to −2) and thoracoabdominal irradiation (TAI, 3Gy x 1 on day −1) (TAI group). The donor was unrelated in 11 patients (8 were genotypically complete matches, and 3 were genotypically DRB1 antigen mismatched) and a family member in 1 patient (3 antigen-mismatched mother). The source of stem cells was unmanipulated bone marrow. Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus (0.02 mg/kg from day −1) and short-term methotrexate. Rejection was seen in one patient in each group. The doses of infused nucleated marrow cells were less than 2.0 x 10 8 /kg in both patients, and both patients then received a second transplant and achieved full donor chimerism. Acute GVHD grade II-IV developed in 2/10 evaluable patients in the TBI group and in 3/12 patients in the TAI group. Chronic GVHD developed in 5/9 evaluable patients in TBI group and 3/10 evaluable patients in TAI group. Median follow up was 9 months (4–27 months) in the TBI group and 21 months (3–33 months) in the TAI group. Both conditioning regimens were well tolerated and effective even in HLA-mismatched unrelated donor transplantation. Long-term follow up is warranted in order to compare the late sequelae in both regimens.


Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 9-12
Author(s):  
RP Gale ◽  
W Ho ◽  
S Feig ◽  
R Champlin ◽  
A Tesler ◽  
...  

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.


Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 9-12 ◽  
Author(s):  
RP Gale ◽  
W Ho ◽  
S Feig ◽  
R Champlin ◽  
A Tesler ◽  
...  

Abstract Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.


1994 ◽  
Vol 12 (6) ◽  
pp. 1217-1222 ◽  
Author(s):  
G Michel ◽  
E Gluckman ◽  
H Esperou-Bourdeau ◽  
J Reiffers ◽  
J L Pico ◽  
...  

PURPOSE To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.


2009 ◽  
Vol 31 (4) ◽  
pp. 595-600 ◽  
Author(s):  
Vicky Sender ◽  
Nicole Hofmeister-Mielke ◽  
Kathrin Sievert ◽  
Jens Peter Teifke ◽  
Heike Vogel ◽  
...  

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