Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens.

1993 ◽  
Vol 11 (2) ◽  
pp. 304-313 ◽  
Author(s):  
J P Radich ◽  
J E Sanders ◽  
C D Buckner ◽  
P J Martin ◽  
F B Petersen ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
High Dose Chemotherapy ◽  
Marrow Transplant ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Allogeneic Marrow Transplantation ◽  
Total Body ◽  
Allogeneic Marrow

PURPOSE The impact of a second marrow transplant on long-term disease-free survival (DFS) was evaluated for 77 consecutive patients aged 2 to 51 years who relapsed subsequent to allogeneic marrow transplantation after high-dose chemotherapy and total-body irradiation (TBI). PATIENTS AND METHODS Patients received a second transplant for recurrent chronic myelogenous leukemia (CML) (n = 28), acute myelogenous leukemia (AML) (n = 32), and acute lymphoblastic leukemia (ALL) (n = 15) or lymphoma (n = 2) that used the same marrow donor as the initial transplant. High-dose chemotherapy of busulfan (BU) and cyclophosphamide (CY), or CY, carmustine (BCNU), and etoposide (VP-16), was used as a preparative regimen for the second transplant. Graft-versus-host disease (GVHD) prophylaxis consisted of the following: no prophylaxis (n = 8), T-cell depletion (n = 36), methotrexate (MTX) only (n = 21), cyclosporine (CSP) only (n = 1), MTX and CSP (n = 9), or anti-thymocyte globulin (ATG) and prednisone (n = 2). RESULTS Engraftment occurred in the 74 assessable patients. Severe veno-occlusive disease (VOD) was the most frequent cause of grades 3 and 4 regimen-related toxicity (RRT); it occurred in 20 patients. The probability of death before day 100 from nonleukemic causes was 36%. The probability of relapse after second transplant was 70%, and the DFS rate was 14% (median DFS, 36 months; range, 22 to 87). The DFS rates for ALL, AML, and CML were 8%, 10%, and 25%, respectively. Multivariate analysis showed that the risk of relapse was inversely associated with acute GVHD (relative risk [RR] of relapse = 0.2; P = .0009). No other factor was associated with relapse. DFS was associated with the presence of acute GVHD (RR of treatment failure = 0.5; P = .0085), and a reduction of DFS was associated with severe VOD (RR = 10.6; P = .0001) and those patients older than 10 years (RR = 2.5; P = .0337). CONCLUSION These data show that some patients may benefit from a second marrow transplant for recurrent leukemia after an initial marrow transplant. Younger patients and patients with CML especially should be considered as potential candidates for a second transplant.

scholarly journals Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1144-1146 ◽  
Author(s):  
JE Sanders ◽  
CD Buckner ◽  
ED Thomas ◽  
R Fleischer ◽  
KM Sullivan ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Family Members ◽  
Myelogenous Leukemia ◽  
Allogeneic Marrow Transplantation ◽  
Total Body ◽  
Allogeneic Marrow

Fourteen children between the ages of 2 and 5 years with juvenile chronic myelogenous leukemia were given cyclophosphamide, total-body irradiation, and marrow transplants. Unmodified marrow was given to six patients who received marrow from HLA-identical siblings and eight patients who received marrow from family members HLA identical for one haplotype but mismatched for one to three loci on the nonshared haplotype. Five patients died of transplant-related complications, and three relapsed at 48, 81, and 1,670 days posttransplant and died of leukemia. Six patients survive in continuous remission from 0.5 to 11.5 years posttransplant.

High-dose chemotherapy, fractionated total-body irradiation, and allogeneic marrow transplantation for malignant lymphoma.

1986 ◽  
Vol 4 (4) ◽  
pp. 480-488 ◽  
Author(s):  
G L Phillips ◽  
R H Herzig ◽  
H M Lazarus ◽  
J W Fay ◽  
R Griffith ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Conventional Therapy ◽  
Allogeneic Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Total Body ◽  
Disease Free ◽  
Allogeneic Marrow

Seventeen patients with malignant lymphoma, including 13 with progressive disease and four in remission following primary chemotherapy, received high-dose chemotherapy, fractionated total-body irradiation (TBI), and allogeneic marrow transplants. Eleven of the 13 (85%) patients in relapse who received transplants achieved remission, and three remain disease free 41, 21, and 17 months later; one patient in second remission who received a transplant is disease free at 11 months. Thirteen patients are dead: four because of progressive lymphoma, seven because of interstitial pneumonitis, and two because of complications of severe acute graft-v-host disease. These results are similar to those noted in marrow transplantation series for advanced acute leukemia; since transplantation during remission has decreased relapse and improved survival in leukemia, earlier transplantation may produce improved results in lymphoma patients as well. However, the effectiveness of conventional therapy regimens for most lymphomas and the high incidence of severe transplant-related complications usually limit allogeneic transplantation to lymphoma patients in situations other than consolidation of first remission. Initial partial remission, early relapse from an initial remission, and perhaps second remission are situations in which conventional therapy is often ineffective, but the adverse features of very advanced lymphoma are not present; marrow transplantation may be considered in eligible patients. Transplant recipients with more advanced disease are anticipated to have poorer survivals.

scholarly journals Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1144-1146 ◽  
Author(s):  
JE Sanders ◽  
CD Buckner ◽  
ED Thomas ◽  
R Fleischer ◽  
KM Sullivan ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Family Members ◽  
Myelogenous Leukemia ◽  
Allogeneic Marrow Transplantation ◽  
Total Body ◽  
Allogeneic Marrow

Abstract Fourteen children between the ages of 2 and 5 years with juvenile chronic myelogenous leukemia were given cyclophosphamide, total-body irradiation, and marrow transplants. Unmodified marrow was given to six patients who received marrow from HLA-identical siblings and eight patients who received marrow from family members HLA identical for one haplotype but mismatched for one to three loci on the nonshared haplotype. Five patients died of transplant-related complications, and three relapsed at 48, 81, and 1,670 days posttransplant and died of leukemia. Six patients survive in continuous remission from 0.5 to 11.5 years posttransplant.

scholarly journals Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1672-1679
Author(s):  
DS Snyder ◽  
RS Negrin ◽  
MR O'Donnell ◽  
NJ Chao ◽  
MD Amylon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Allogeneic Bone ◽  
Total Body

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.

scholarly journals Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens [see comments]

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1867-1871 ◽  
Author(s):  
RA Clift ◽  
CD Buckner ◽  
FR Appelbaum ◽  
SI Bearman ◽  
FB Petersen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Randomized Trial ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Allogeneic Marrow Transplantation ◽  
First Remission ◽  
Total Body ◽  
Allogeneic Marrow ◽  
Acute Myeloid

Abstract A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3-year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHD was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse.

Allogeneic marrow transplantation using fractionated total body irradiation in patients with acute lymphoblastic leukemia in relapse

1982 ◽  
Vol 6 (3) ◽  
pp. 401-407 ◽  
Author(s):  
Reginald A. Clift ◽  
C. Dean Buckner ◽  
E. Donnall Thomas ◽  
Jean E. Sanders ◽  
Patricia S. Stewart ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Marrow Transplantation ◽  
Total Body ◽  
Allogeneic Marrow

scholarly journals Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1672-1679 ◽  
Author(s):  
DS Snyder ◽  
RS Negrin ◽  
MR O'Donnell ◽  
NJ Chao ◽  
MD Amylon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Allogeneic Bone ◽  
Total Body

Abstract Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.

scholarly journals Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens [see comments]

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1867-1871 ◽  
Author(s):  
RA Clift ◽  
CD Buckner ◽  
FR Appelbaum ◽  
SI Bearman ◽  
FB Petersen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Randomized Trial ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Allogeneic Marrow Transplantation ◽  
First Remission ◽  
Total Body ◽  
Allogeneic Marrow ◽  
Acute Myeloid

A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3-year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHD was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse.

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