Prognostic Factors for Leukemic Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study

Oudot, Caroline; Auclerc, Marie-Françoise; Lévy, Vincent; Porcher, Raphaël; Piguet, Christophe; Pérel, Yves; Gandemer, Virginie; Debré, Marianne; Vermylen, Christiane; Pautard, Brigitte; Berger, Claire; Schmitt, Claudine; Leblanc, Thierry; Cayuela, Jean‐Michel; Socié, Gérard; Gautier, Michel; Leverger, Guy; Baruchel, André

doi:10.1200/jco.2007.12.2820

Cited by 95 publications

(70 citation statements)

References 64 publications

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“…It is largely accepted that translocations t(4;11) and t(9;22) identify patients at high risk of treatment failure. 33,34 In our analysis, LFS at 4 years did not differ among the 63 patients with unfavorable and the 85 patients with favorable or intermediate cytogenetics (47% vs 52%, P ¼ 0.23).…”

Section: Discussionmentioning

confidence: 46%

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

et al. 2012

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To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) ¼ 0.4, P ¼ 0.01) and for those transplanted in CR1 and CR2 (HR ¼ 0.3, P ¼ 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P ¼ 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR ¼ 2, P ¼ 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.

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Section: Discussionmentioning

confidence: 46%

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

et al. 2012

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“…Patients were treated in accordance with current protocol at the time of leukemia diagnosis, depending on AL type (AML or ALL; that is, FRench group for childhood ALL (FRALLE), European Organisation for Research and Treatment of Cancer (EORTC), Leucémie Aiguë Myéloblastique Enfant (LAME) or ELAM). [19][20][21][22][23] Overall, 16 patients underwent central nervous system irradiation.…”

Section: Patient Characteristicsmentioning

confidence: 99%

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study

Oudin

Auquier

Bertrand

et al. 2015

Bone Marrow Transplant

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We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8 ± 5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n = 119, or AML, n = 51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P = 0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P = 0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P = 0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P = 0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis.

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“…12,13,[29][30][31][32][33][34] Specificity of response evaluation might, nevertheless, vary depending on the time of response evaluation with regard to the therapy and the composition of the treatment. 13,35,36 With the aim of prospectively assessing the prognostic value of an early cytomorphological response evaluation in the BM, a BM puncture on Day 15 of induction treatment was performed in addition to the evaluation of PR and BMd33 in ALL-BFM 95.…”

confidence: 99%

Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia

Lauten¹,

Möricke²,

Beier³

et al. 2012

Haematologica

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BackgroundIn the ALL-BFM 95 trial for treatment of acute lymphoblastic leukemia, response to a prednisone pre-phase (prednisone response) was used for risk stratification in combination with age and white blood cell count at diagnosis, response to induction therapy and specific genetic high-risk features. Design and MethodsCytomorphological marrow response was prospectively assessed on Day 15 during induction, and its prognostic value was analyzed in 1,431 patients treated on ALL-BFM 95. ResultsThe 8-year probabilities of event-free survival were 86.1%, 74.5%, and 46.4% for patients with M1, M2, and M3 Day 15 marrows, respectively. Compared to prednisone response, Day 15 marrow response was superior in outcome prediction in precursor B-cell and T-cell leukemia with, however, a differential effect depending on blast lineage. Outcome was poor in T-cell leukemia patients with prednisone poor-response independent of Day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by Day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B-cell leukemia when stratified by Day 15 marrow response. Age and white blood cell count retained their independent prognostic effect. ConclusionsSelective addition of Day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 (currently in use in several countries as regular chemotherapy protocol for childhood acute lymphoblastic leukemia) may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries that lack the technical and/or financial resources associated with the application of minimal residual disease analysis.Key words: pediatric acute lymphoblastic leukemia, early treatment response, clinical trial. -cell and T-cell leukemia. Haematologica 2012;97(7):1048-1056. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Lauten M, Möricke A, Beier R, Zimmermann M, Stanulla M, Meissner B, Odenwald E, Attarbaschi A, Niemeyer C, Niggli F, Riehm H, and Schrappe M. Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor BPrediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia © F e r r a t a S t o r t i F o u n d a t i o n

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Prognostic Factors for Leukemic Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study

Abstract: Three risk categories for LIF in children with ALL were identified. Approximately one third of patients with LIF can be successfully treated with salvage therapy overall. Subsequent CR after LIF is mandatory for cure.

Cited by 95 publications

References 64 publications

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study

Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia

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