Age-adapted induction treatment of acute lymphoblastic leukemia in the elderly and assessment of maintenance with interferon combined with chemotherapy. A multicentric prospective study in forty patients

Delannoy, André; Sebban, Catherine; Cony‐Makhoul, Pascale; Cazin, Bruno; Cordonnier, Catherine; Bouabdallah, Réda; Cahn, J; Dreyfus, François; Sadoun, A.; Jp, Vernant; Gay, Caroline; Broustet, A; Michaux, Jl.; Fière, D

doi:10.1038/sj.leu.2400780

Cited by 38 publications

(28 citation statements)

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“…Similarly disappointing results were reported with interferon-␣ maintenance therapy given with or without concomitant chemotherapy in first CR of ALL. 45,46 However, the latter study included patients older than 50 years, with a higher percentage of Ph ϩ patients.…”

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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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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“…been due in part to the slight imbalance in favor of more T-ALL in the Peg-Dox arm, although this feature was not identified as a poor prognostic indicator in previous studies of ALL patients over 60 years old. 1,2,4,7,24,28,[30][31][32][33][34][35][36][37][38][39][40] Another explanation may be an incorrect calculation of the PegDox dose equivalence. As no pharmacokinetic studies were available comparing CI-Dox to Peg-Dox, the PegDox dose was defined according to the pivotal randomized study in metastatic breast cancer 15 and studies performed in high-grade non-Hodgkin's lymphoma 41,42 which applied a 1.2 dose reduction factor between conventional doxorubicin and Peg-Dox, the total conventional doxorubicin dose being divided over 4 days in the CI arm.…”

Section: Discussionmentioning

confidence: 99%

A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

Hunault¹,

Leguay²,

Thomas

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia. Design and MethodsSixty patients received either continuous-infusion doxorubicin (12 mg/m 2 /day) and continuousinfusion vincristine (0.4 mg/day) on days 1-4 or pegylated liposomal doxorubicin (40 mg/m 2 ) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors. ResultsMyelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm. ConclusionsWith the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities. (ClinicalTrials.gov Identifier: NCT00600977).

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“…Therefore, induction therapy is the most critical phase for management. In older patients, induction mortality has a wide range (0% to 42%) ( Table 1 1,4-6,11,14,15, [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] ). Seven percent to 10% of older patients die even before initiation of chemotherapy.…”

Section: Induction Therapymentioning

confidence: 99%

“…14,28, [51][52][53][54][55][56]64 One central question is whether and which anthracycline needs to be included in induction regimens for older patients since these drugs contribute considerably to bone marrow toxicity. One approach is the use of idarubicine in induction therapy based on its supposed lower cardiac and hepatic toxicity.…”

Section: Prospective Studies For Older All Patientsmentioning

confidence: 99%

How I treat older patients with ALL

Gökbuget

2013

Blood

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The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. In Western countries, the population is aging, which means there will be an increasing number of older patients. However, in the past few decades, there has been little improvement in treating them, and few clinical trials specifically designed for older patients with ALL have been reported. Older patients with ALL have a significantly lower complete response rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is partly explained by a higher incidence of poor prognostic factors. Most importantly, intensive chemotherapy with or without stem cell transplantation, both of which are successful in younger patients, is less well tolerated in older patients. For the future, the most promising approaches are optimized supportive care, targeted therapies, moderately intensified consolidation, and reduced-intensity stem cell transplantation. One of the most important challenges for physicians is to differentiate between fit and unfit older patients in order to offer both groups optimal treatment regarding toxicity and mortality risks, quality of life, and long-term outcome. Prospective trials for older patients with ALL are urgently needed.

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Age-adapted induction treatment of acute lymphoblastic leukemia in the elderly and assessment of maintenance with interferon combined with chemotherapy. A multicentric prospective study in forty patients

Cited by 38 publications

References 1 publication

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

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

A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

How I treat older patients with ALL

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