Bone marrow transplantation versus chemotherapy in the treatment of very high–risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2412-2418
Author(s):  
Kate A. Wheeler ◽  
Susan M. Richards ◽  
Clifford C. Bailey ◽  
Brenda Gibson ◽  
Ian M. Hann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Marrow Transplantation ◽  
Research Council ◽  
Medical Research Council ◽  
Lymphoblastic Leukemia ◽  
First Remission ◽  
Very High

The role of bone marrow transplantation (BMT) in first remission of children with high-risk acute lymphoblastic leukemia (ALL) remains unclear. There were 3676 patients (aged 1 to 15 years) entered into the United Kingdom (UK) Medical Research Council (MRC) trials UKALL X and XI from 1985 to 1997. Of these patients, 473 patients (13%) were classified as very high (VH) risk and were eligible for a transplantation from a matched histocompatible sibling donor (MSD). We tissue-typed 286 patients; 99 patients had a matched related donor, and 76 patients received transplantations. Additionally, 25 children received transplantations from a matched unrelated donor (MUD) despite trial guidelines for MSD transplantations only. The median time to transplantation was 5 months (range, 2 to 19 months), and the median follow-up was 8 years. The 10-year event-free survival (EFS) adjusted for the time to transplantation, diagnostic white blood cell (WBC) count, Ph chromosome status, and ploidy was 6.0% higher (95% confidence interval (CI), −10.5% to 22.5%) for 101 patients who received a first-remission transplantation (MSD and MUD) than for the 351 patients treated with chemotherapy (transplantation, 45.3%, vs chemotherapy, 39.3%). The transplantation group had fewer relapses (31%) compared to relapses in the chemotherapy group (55%); however, the transplantation group had more remission deaths (18%) compared to remission deaths in the chemotherapy group (3%). In contrast the adjusted 10-year EFS was 10.7% higher (95% CI, −2.6% to 24.0%) for patients without a human leukocyte antigen (HLA)–matched donor than for those patients with a donor (no donor, 50.4%, vs donor, 39.7%). In conclusion, for the majority of children with VH-risk ALL, the first-remission transplantation has not improved EFS.

Bone marrow transplantation versus chemotherapy in the treatment of very high–risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2412-2418 ◽  
Author(s):  
Kate A. Wheeler ◽  
Susan M. Richards ◽  
Clifford C. Bailey ◽  
Brenda Gibson ◽  
Ian M. Hann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Marrow Transplantation ◽  
Research Council ◽  
Medical Research Council ◽  
Lymphoblastic Leukemia ◽  
First Remission ◽  
Very High

Abstract The role of bone marrow transplantation (BMT) in first remission of children with high-risk acute lymphoblastic leukemia (ALL) remains unclear. There were 3676 patients (aged 1 to 15 years) entered into the United Kingdom (UK) Medical Research Council (MRC) trials UKALL X and XI from 1985 to 1997. Of these patients, 473 patients (13%) were classified as very high (VH) risk and were eligible for a transplantation from a matched histocompatible sibling donor (MSD). We tissue-typed 286 patients; 99 patients had a matched related donor, and 76 patients received transplantations. Additionally, 25 children received transplantations from a matched unrelated donor (MUD) despite trial guidelines for MSD transplantations only. The median time to transplantation was 5 months (range, 2 to 19 months), and the median follow-up was 8 years. The 10-year event-free survival (EFS) adjusted for the time to transplantation, diagnostic white blood cell (WBC) count, Ph chromosome status, and ploidy was 6.0% higher (95% confidence interval (CI), −10.5% to 22.5%) for 101 patients who received a first-remission transplantation (MSD and MUD) than for the 351 patients treated with chemotherapy (transplantation, 45.3%, vs chemotherapy, 39.3%). The transplantation group had fewer relapses (31%) compared to relapses in the chemotherapy group (55%); however, the transplantation group had more remission deaths (18%) compared to remission deaths in the chemotherapy group (3%). In contrast the adjusted 10-year EFS was 10.7% higher (95% CI, −2.6% to 24.0%) for patients without a human leukocyte antigen (HLA)–matched donor than for those patients with a donor (no donor, 50.4%, vs donor, 39.7%). In conclusion, for the majority of children with VH-risk ALL, the first-remission transplantation has not improved EFS.

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia in remission: prolonged survival associated with acute graft-versus-host disease.

1987 ◽  
Vol 5 (9) ◽  
pp. 1348-1355 ◽  
Author(s):  
D J Weisdorf ◽  
M E Nesbit ◽  
N K Ramsay ◽  
W G Woods ◽  
A I Goldman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Maintenance Chemotherapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Acute Graft

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.

scholarly journals Autologous bone marrow transplantation after a long first remission for children with recurrent acute lymphoblastic leukemia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1651-1657 ◽  
Author(s):  
AL Billett ◽  
E Kornmehl ◽  
NJ Tarbell ◽  
HJ Weinstein ◽  
RD Gelber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Free Survival ◽  
First Remission ◽  
Autologous Bone

Abstract Fifty-one children with acute lymphoblastic leukemia (ALL) in second or subsequent remission after a first remission of at least 24 months underwent purged, autologous bone marrow transplantation (ABMT). Bone marrow was harvested in remission and purged in vitro with monoclonal antibodies specific for leukemia-associated antigens. Ablative chemotherapy included cytarabine, teniposide, and cyclophosphamide followed by total body irradiation. Of the 51 patients treated between November 1980 and June 1991, 5 died of treatment-related complications, 18 relapsed, 1 died of a second tumor at 6.7 years, and 27 remained in continuous complete remission for a median of 39 months (range, 9+ to 124+). Event-free survival (EFS) (+/- SE) at 3 years after ABMT was 53% +/- 7%. Leukemia-free survival (LFS) was 58% +/- 8%. In multivariate analysis, the most significant predictors of EFS were duration of longest pre-ABMT remission and remission duration immediately before ABMT. For LFS, the most significant predictors were cell dose per kilogram of marrow reinfused and duration of longest pre-ABMT remission. We conclude that ABMT for this population is an effective therapy available to the majority of children with relapsed ALL.

scholarly journals Autologous bone marrow transplantation after a long first remission for children with recurrent acute lymphoblastic leukemia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1651-1657 ◽  
Author(s):  
AL Billett ◽  
E Kornmehl ◽  
NJ Tarbell ◽  
HJ Weinstein ◽  
RD Gelber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Free Survival ◽  
First Remission ◽  
Autologous Bone

Fifty-one children with acute lymphoblastic leukemia (ALL) in second or subsequent remission after a first remission of at least 24 months underwent purged, autologous bone marrow transplantation (ABMT). Bone marrow was harvested in remission and purged in vitro with monoclonal antibodies specific for leukemia-associated antigens. Ablative chemotherapy included cytarabine, teniposide, and cyclophosphamide followed by total body irradiation. Of the 51 patients treated between November 1980 and June 1991, 5 died of treatment-related complications, 18 relapsed, 1 died of a second tumor at 6.7 years, and 27 remained in continuous complete remission for a median of 39 months (range, 9+ to 124+). Event-free survival (EFS) (+/- SE) at 3 years after ABMT was 53% +/- 7%. Leukemia-free survival (LFS) was 58% +/- 8%. In multivariate analysis, the most significant predictors of EFS were duration of longest pre-ABMT remission and remission duration immediately before ABMT. For LFS, the most significant predictors were cell dose per kilogram of marrow reinfused and duration of longest pre-ABMT remission. We conclude that ABMT for this population is an effective therapy available to the majority of children with relapsed ALL.

Allogeneic Bone Marrow Transplantation Versus Chemotherapy for the Treatment of Childhood Acute Lymphoblastic Leukemia in Second Remission: A Single-Institution Study

1999 ◽  
Vol 17 (1) ◽  
pp. 197-197 ◽  
Author(s):  
Farid Boulad ◽  
Peter Steinherz ◽  
Bernadette Reyes ◽  
Glenn Heller ◽  
Alfred P. Gillio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Single Institution ◽  
First Remission ◽  
Wbc Count

PURPOSE: A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively RESULTS: The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 × 109/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 × 109/L (DFS, 73% v 35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%). CONCLUSION: In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.

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