Long-term follow-up of intensive ara-C-based chemotherapy followed by bone marrow transplantation for adult acute lymphoblastic leukemia: impact of induction Ara-C dose and post-remission therapy

Sotomayor, Eduardo M.; Piantadosi, Steven; Miller, Carole B.; Karp, JE; Jones, Richard J.; Rowley, Scott D.; Kaufmann, Scott H.; Braine, HG; Burke, Philip J.; Gore, Steven D.

doi:10.1016/s0145-2126(01)00175-8

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…Maintenance, in general, is still standard for ALL patients, since all attempts to omit it have led to inferior long-term outcome with LFS rates of 18-28% [1]. It can be assumed that our results for autoHSCT would be worse without maintenance therapy, a view that concurs with the data published by Sotomayor et al [22] and Mehta et al [23]. The question still remains, though, whether to further increase the dose of maintenance would lead to even better results [24].…”

Section: Discussionsupporting

confidence: 87%

Autologous hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: still not out of fashion

et al. 2009

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The role of autologous hematopoietic stem cell transplantation (autoHSCT) in adult acute lymphoblastic leukemia (ALL) is still unclear. We retrospectively analyzed the results of the autoHSCT and maintenance therapy, with oral 6-mercaptopurine and methotrexate, in comparison to conventional-dose chemotherapy in the consolidation treatment of adult ALL and lymphoblastic lymphoma (LBL). The patients, with HLA identical sibling donor, underwent allogeneic transplantation, while the others were treated with autoHSCT and maintenance therapy with oral 6-mercaptopurine and methotrexate, or by conventionaldose chemotherapy (patient's decision, no autologous hematopoietic stem cells harvest). Sixty consecutive adult patients (median age 35.2 years; range 17.3 to 70.7) with ALL (n=52), LBL (n=7), and acute biphenotypic leukemia (n=1) were treated in our center from 1997 to 2007. Patients treated with chemotherapy alone (n=35) had a shorter median progression-free survival (PFS) compared to patients who underwent autoHSCT plus maintenance therapy (n=18), 8.4 and 46.8 months, respectively (p= 0.017). Patients treated with chemotherapy alone had also a shorter median overall survival (OS) compared to patients treated with autoHSCT: 13.0 vs. 46.8 months (p=0.046). The differences remained statistically significant even after excluding patients with Ph positivity. We can conclude that, in our case, autoHSCT followed by maintenance chemotherapy is a good option for adult patients with ALL and, in standard-risk and high-risk patients, provides more favorable OS and PFS rates compared to patients treated by chemotherapy alone. However, we are aware of the fact that our analysis may have been distorted by the fact that the analysis is retrospective, that treatment with autoHSCT was based on patient's decision, and that chemotherapy may have been administered to negatively selected patients.

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Section: Discussionsupporting

confidence: 87%

Autologous hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: still not out of fashion

et al. 2009

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“…8,28 Translocation t(9;22) or BCR/ABL rearrangement decreased the CR rate (54%) as reported. 6,17,21,29, 30 The prognostic impact of T-lineage ALL [31][32][33] could not be ascertained, as young patients who had T-ALL with WBC count less than 30 ϫ 10 9 /L were not included.…”

Section: Discussionmentioning

confidence: 99%

Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial

Hunault

Harousseau²,

Delain³

et al. 2004

Blood

221

150

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, for the GOELAMS (Groupe Ouest-Est des Leucé mies Aiguë s et Maladies du Sang) GroupVarious transplantation strategies have been designed to improve the poor prognosis of adult (ages 15 to 60 years) acute lymphoblastic leukemia (ALL). The GOELAL02 trial evaluated the impact of early allogeneic bone marrow transplantation (alloBMT) or delayed unpurged autologous stem cell transplantation (ASCT) for patients who had no human leukocyte antigen (HLA)-matched sibling donor or who were older than 50 years. Inclusion criteria included at least one of the following: age older than 35 years; non-T-ALL; leukocytosis greater than 30 ؋ 10 9 /L; t(9;22), t(4;11), or t(1; 19); or failure to achieve complete remission (CR) after one induction course. Among 198 patients, the median age was 33 years. The CR rate was 80% with vincristine, idarubicine, L-asparaginase, and randomized intravenous injection or oral steroids (P ‫؍‬ nonsignificant [ns]). AlloBMT was performed after 2 consolidation courses while ASCT was delayed after 1 additional reinduction. Intensified conditioning regimen before transplantation included etoposide, cyclophosphamide, and total body irradiation (TBI). Median follow-up was 5.1 years. The median overall survival (OS) was 29 months, with a 6-year OS of 41%. On an intent-to-treat analysis for patients younger than 50 years, alloBMT significantly improved the 6-year OS (75% versus 40% after ASCT; P ‫؍‬ .0027). Randomized interferon-␣ maintenance had no effect on relapse or survival after ASCT. In conclusion, the outcome of adult ALL is better after early alloBMT than after delayed ASCT. (Blood. 2004; 104:3028-3037)

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“…We have attempted to improve 1 the relatively poor results of high-dose therapy and autotransplantation in adult acute lymphoblastic leukemia (ALL) [2][3][4][5][6][7][8][9][10][11][12][13][14][15] by administering maintenance chemotherapy with 6-mercaptopurine (6MP), methotrexate (MTX) and vincristine-prednisone (VP) for 2 years after transplantation. The results, using melphalan with total-body irradiation (TBI) and autologous bone marrow initially and high-dose melphalan alone with blood-derived stem cells subsequently, have been very encouraging and strongly suggest that post transplant maintenance chemotherapy is useful.…”

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confidence: 99%

High-dose melphalan and autotransplantation followed by post transplant maintenance chemotherapy for acute lymphoblastic leukemia in first remission

Mehta

Powles

Sirohi

et al. 2004

Bone Marrow Transplant

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Summary:A total of 65 adults with acute lymphoblastic leukemia (ALL) received 200 mg/m 2 melphalan and an autograft in first remission, with a plan to receive 6-mercaptopurine (6MP), methotrexate (MTX), and vincristine-prednisone (VP) for 2 years afterwards. There was no transplantrelated mortality. In all, 69% of patients received 6MP, 54% received MTX, and 49% received VP. The cumulative incidence of relapse at 5 years was 52%.The 5-year probabilities of disease-free (DFS) and overall (OS) survival were 48 and 55%. Age 430 years, 44 weeks to attain remission, and t(9;22) or t(4;11) karyotypes were adverse prognostic features. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 5-year cumulative incidences of relapse of 19, 59, and 100% (Po0.0001), and 5-year probabilities of DFS of 80, 41, and 0% (Po0.0001). The 5-year probabilities of DFS for patients receiving 0, 1, 2, and 3 maintenance therapy agents were 19, 40, 51, and 70% (P ¼ 0.0097). Maintenance therapy intensity was an independent determinant of outcome in Cox analysis. These data show that a high-dose melphalan-based autograft is safe and could be widely applicable in ALL in first remission, and that maintenance chemotherapy very likely contributes to improved outcome of autografted ALL patients. 2-15 by administering maintenance chemotherapy with 6-mercaptopurine (6MP), methotrexate (MTX) and vincristine-prednisone (VP) for 2 years after transplantation. The results, using melphalan with total-body irradiation (TBI) and autologous bone marrow initially and high-dose melphalan alone with blood-derived stem cells subsequently, have been very encouraging and strongly suggest that post transplant maintenance chemotherapy is useful.

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Long-term follow-up of intensive ara-C-based chemotherapy followed by bone marrow transplantation for adult acute lymphoblastic leukemia: impact of induction Ara-C dose and post-remission therapy

Cited by 11 publications

References 41 publications

Autologous hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: still not out of fashion

Autologous hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: still not out of fashion

Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial

High-dose melphalan and autotransplantation followed by post transplant maintenance chemotherapy for acute lymphoblastic leukemia in first remission

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