scholarly journals Allogeneic bone marrow transplantation (BMT) for the treatment of children with very high risk acute lymphoblastic leukemia (ALL) in first remission (CR1)

2004 ◽  
Vol 10 ◽  
pp. 26
Author(s):  
F. Boulad ◽  
P. Steinherz ◽  
N.A. Kernan ◽  
T.N. Small ◽  
V. Prasad ◽  
...  
Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2412-2418
Author(s):  
Kate A. Wheeler ◽  
Susan M. Richards ◽  
Clifford C. Bailey ◽  
Brenda Gibson ◽  
Ian M. Hann ◽  
...  

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.


Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2412-2418 ◽  
Author(s):  
Kate A. Wheeler ◽  
Susan M. Richards ◽  
Clifford C. Bailey ◽  
Brenda Gibson ◽  
Ian M. Hann ◽  
...  

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.


1999 ◽  
Vol 17 (1) ◽  
pp. 197-197 ◽  
Author(s):  
Farid Boulad ◽  
Peter Steinherz ◽  
Bernadette Reyes ◽  
Glenn Heller ◽  
Alfred P. Gillio ◽  
...  

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.


1995 ◽  
Vol 13 (2) ◽  
pp. 352-358 ◽  
Author(s):  
C Uderzo ◽  
M G Valsecchi ◽  
A Bacigalupo ◽  
G Meloni ◽  
C Messina ◽  
...  

PURPOSE To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.


1988 ◽  
Vol 34 (12) ◽  
pp. 2586-2588 ◽  
Author(s):  
B Grahovac ◽  
B Labar ◽  
A Stavijenić

Abstract We report an effective follow-up of the establishment of bone-marrow function after an allogeneic bone-marrow transplantation in a patient with acute lymphoblastic leukemia, by means of a suitable genetic marker, phosphoglucomutase-1 (EC 5.4.2.2) isoenzyme. A patient with acute lymphoblastic leukemia received allogeneic bone-marrow graft from a sibling who was of the same sex and blood group, HLA-identical, and mixed-lymphocyte-culture nonreactive. To monitor the bone-marrow engraftment and the type and degree of chimerism established, we used a genetic marker, the phosphoglucomutase-1 isoenzyme system, to reveal the difference between the bone-marrow host and donor. We did phosphoglucomutase-1 isoenzyme subtyping of the host's and donor's erythrocytes before transplantation, and isoenzyme phenotyping of the host's erythrocytes during a year after transplantation. Establishment of bone-marrow graft function, a period of temporary mixed chimerism with a population of both host's and donor's erythrocytes, a period of the exclusive presence of donor's erythrocytes, and the resumed appearance of host's erythrocytes after eight months, with no signs of relapse of leukemia, were all observed by analysis of phenotypes. These isoenzymes served as a significant and practical genetic marker, which could be successfully used in studies on bone-marrow transplantation.


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