Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome–positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study

Labarthe, Adrienne de; Rousselot, Philippe; Huguet-Rigal, Françoise; Delabesse, Éric; Witz, Francis; Maury, Sébastien; Réa, Delphine; Cayuela, Jean‐Michel; Vekemans, Marie-Christine; Reman, Oumédaly; Buzyn, Agnès; Pigneux, Arnaud; Escoffre, Martine; Chalandon, Yves; Macintyre, Elizabeth; Lhéritier, Véronique; Vernant, Jean‐Paul; Thomas, Xavier; Ifrah, Norbert; Dombret, Hervé

doi:10.1182/blood-2006-03-011908

Cited by 298 publications

(215 citation statements)

References 17 publications

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“…The combination of imatinib with conventional chemotherapy as the first-line treatment has demonstrated an improved CR rate and an increased applicability in allogeneic SCT, thus allowing better outcomes in adults with Ph-positive ALL [33][34][35][36][37]. Previously, we also conducted a prospective, phase II trial of allogeneic SCT following firstline imatinib-based chemotherapy, and our recently updated results continue to show the positive impact of imatinib on long-term outcomes of allogeneic SCT [21][22][23].…”

Section: Discussionmentioning

confidence: 88%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

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The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P 5 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P 5 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P 5 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634-641,

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Section: Discussionmentioning

confidence: 88%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

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“…[1][2][3][4][5][6] However, with an extended follow-up, a substantial proportion of transplant patients and practically almost all non-transplant patients continue to die as a result of relapse. Consequently, patients at the highest risk of relapse are likely to benefit from the identification of new criteria that enable predictable patient outcome.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] Most published studies in the imatinib era include quantitative MRD findings, [1][2][3][4][5][6] but the longterm outcome in relation to molecular response to any given therapeutic approach remains to be determined. Previously, we conducted a prospective, phase 2 trial of allogeneic SCT following first-line imatinib-based chemotherapy in adults with Ph-positive ALL, and in the trial, BCR-ABL1 transcript levels in the bone marrow (BM) were routinely monitored using real-time quantitative PCR (RQ-PCR).…”

Section: Introductionmentioning

confidence: 99%

Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

et al. 2012

Leukemia

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We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinibbased chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n ¼ 33), late molecular responders (LMRs, n ¼ 35), intermediate molecular responders (IMRs, n ¼ 9) and poor molecular responders (PMRs, n ¼ 18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.

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“…Imatinib has recently been used in adult patients with Ph þ ALL in conjunction with standard chemotherapy and allo-HCT with mixed results reported. [8][9][10][11] Thus, the utility of imatinib in either the pre-or post-transplant period for Ph þ ALL remains uncertain. In addition, there have been concerns regarding imatinib and cardiac toxicity, notably congestive heart failure (CHF), in both preclinical studies and some clinical series.…”

Section: Introductionmentioning

confidence: 99%

Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival

Burke

Trotz

Luo

et al. 2008

Bone Marrow Transplant

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The utility of imatinib in either the pre-or post-transplant period for Ph chromosome-positive (Ph þ ) ALL is uncertain. In addition, there have been recent concerns regarding imatinib and cardiac toxicity. We investigated the outcome of 32 patients with Ph þ ALL who received an allo-hematopoietic cell transplant (HCT) at the University of Minnesota between 1999 and 2006. The median age at HCT was 21.9 years (range: 2.8-55.2). All patients were conditioned with CY and TBI. GVHD prophylaxis was CsA based. Of the 32 patients, 15 received imatinib therapy pre-or post-HCT (imatinib group) and 17 patients received either no imatinib (n ¼ 11) or only after relapse (n ¼ 6) (non-imatinib group). Overall survival, relapse-free survival and relapse at 2 years was 61, 67 and 13% for the imatinib group as compared with 41, 35 and 35% for the non-imatinib group (P ¼ 0.19, 0.12 and 0.20, respectively). Cardiac toxicity and TRM at 2 years were similar between groups. Thus, patients treated with imatinib in either the pre-or post-transplant setting had trends toward improved outcomes and no increase in cardiac toxicity. We suggest that imatinib be included in the peri-transplant management of all patients with Ph þ ALL.

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Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome–positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study

Cited by 298 publications

References 17 publications

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival

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