Maël Heiblig

Major Molecular Response Achievement in CML Patients Can Be Predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS Ratio at an Earlier Time Point of Follow-Up than Currently Recommended

Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy. In this study, we evaluated the ability of the control gene GUS to identify relevant thresholds for known therapeutic decision levels (BCR-ABL1/ABL1IS  = 10% and 0.1%). We then defined the most relevant cut-offs for early molecular response markers (transcript level at 3 months, halving time and log reduction between diagnosis and 3 months of treatment) using GUS or ABL1. We demonstrated that, although both control genes could be used (in an equivalent way) to accurately assess early molecular response, the BCR-ABL1/GUS level at diagnosis is impacted by the higher GUS copy number over-expressed in CML cells, thus negatively impacting its ability to completely replace ABL1 at diagnosis. Furthermore, we pointed out, for the first time, that it would be helpful to monitor BCR-ABL1 levels at an earlier time point than that currently performed, in order to assess response to first-line tyrosine-kinase inhibitors and consider a potential switch of therapy as early as possible. We evaluated this optimal time point as being 19 days after the start of treatment in our cohort.

Hyperhomocysteinemia and high doses of nilotinib favor cardiovascular events in chronic phase Chronic Myelogenous Leukemia patients

In chronic phase chronic myeloid leukemia (CP-CML), nilotinib (Tasigna®, Novartis, second-generation tyrosine kinase inhibitor, TKI2) as second-line therapy1 results in successful responses and tolerance in ~50% of patients in the long-term.2 As a consequence, some patients have been on nilotinib for approximately 9–10 years now. Recently, nilotinib, introduced as first-line treatment, induced superior cytogenetic and molecular responses and significantly decreased the risk of progression,3 and has been approved in this setting since 2010.

Effect of Initial Body Mass Index on Survival Outcome of Patients With Acute Leukemia: A Single-Center Retrospective Study

BACKGROUND Obesity is associated with an increased risk of mortality from cardiovascular causes and occurrence of malignancies. However, the effect of body mass index (BMI) on survival outcome remains controversial in acute leukemia (AL) patients. PATIENTS AND METHODS A total of 531 adults with AL who entered clinical trials in our institution between 1994 and 2012 were analyzed retrospectively for the effect of BMI at diagnosis on outcome. The median follow-up was 4.7 years (95% confidence interval [CI], 4.0-5.1). RESULTS BMI had no significant effect on complete response rate, disease-free survival (DFS), or overall survival (OS) in patients from the whole cohort when considering a cutoff value for BMI of 25, and when analyzed according to age, or initial cytogenetics. In T-acute lymphoblastic leukemia (T-ALL) patients with BMI > 25, median DFS was not reached with a 3-year DFS at 76%, and median DFS was 16.1 months with 3-year DFS at 13% for those with BMI ≤ 25 (P = .005). Median OS was not reached in T-ALL patients with BMI > 25 versus 28.3 months in those with BMI ≤ 25 (3-year OS: 78% vs. 41%; P = .04). Multivariate analyses confirmed the prognostic value of BMI (> 25 vs. < 25) in T-ALL, but only in terms of DFS (hazard ratio, 0.25; 95% CI, 0.05-0.87; P = .037). However, in a validation cohort of 211 T-ALL patients, these results were not confirmed. CONCLUSION Results from the literature are very heterogeneous and contradictory regarding the effect of BMI on leukemia outcome. Even if nutritional status during chemotherapy courses is critical, these findings provide further evidence that initial body size does not have a major prognostic effect on survival in AL patients.

Treatment patterns and comparative effectiveness in elderly acute myeloid leukemia patients (age 70 years or older): the Lyon-university hospital experience

Abstract The treatment of very elderly patients (≥70 years) with acute myeloid leukemia remains controversial. We present here 302 patients seen over a 14-year period in order to understand the real-world treatment patterns and outcomes in this patient population. Less than 25% of patients achieved a complete remission. The median overall survival was 12.4, 11.5 and 2.6 months, with a 3-year rates of 27%, 17% and 6%, for non-acute promyelocytic leukemia patients receiving intensive chemotherapy, lower-intensity therapy or best supportive care (BSC), respectively. In all ages, results were not significantly different among patients receiving low-intensity therapy and intensive chemotherapy, but significantly worse in those treated with BSC only. Similarly, intensive chemotherapy and low-intensity therapy gave better survival rates than BSC in patients with favorable- or intermediate-risk cytogenetics and in those with unfavorable cytogenetics (p < 0.0001 and p = 0.04, respectively).

Acute myeloid leukemia in the elderly (age 70 yr or older): long‐term survivors

Little data exist regarding long‐term survival in elderly patients with acute myeloid leukemia (AML).

Comprehensive analysis of a myeloperoxidase-negative acute promyelocytic leukemia

To the editor: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), characterized by the t(15;17) translocation resulting in the PML-RARA fusion transcript. The use of all-trans retinoic acid (ATRA) and/or arsenic has revolutionized the treatment of this disease, which

Elderly Patients (Age 70 Years or Older) With Secondary Acute Myeloid Leukemia or Acute Myeloid Leukemia Developed Concurrently to Another Malignant Disease

Micro‐Abstract This study gives a detailed description of acute myeloid leukemia (AML) following another malignancy in a single‐center cohort of patients with AML aged 70 and older. The most important finding is the lack of independent prognostic impact of secondary AML in elderly patients. Introduction Secondary acute myeloid leukemia (sAML) remains a therapeutic challenge. In elderly patients with AML, it is unclear whether sAML displays an inferior outcome compared with de novo AML. Patients and Methods We studied AML with an antecedent of hematologic disease, treatment‐related AML, or AML occurring concurrently to another malignancy in a single‐center cohort of patients aged 70 and older with AML. The study included 169 patients who were compared with a cohort of patients with de novo AML, without any prior history of malignant disorders, seen during the same period of time. Results Hematologic antecedents or presence of prior/concurrent solid malignancy did not impact complete remission rates and overall survival. In multivariate analysis, sAML appeared without independent prognostic value in the elderly. Conclusion Our results support that sAML and de novo AML in elderly patients are not prognostically distinct entities. They should therefore not be considered separately when investigating outcomes and new treatment strategies.

Allogeneic anti-CD19 CAR T cells: new perspectives in the treatment of B-cell malignancies that progress after allogeneic stem cell transplantation?

Allogeneic stem cell transplantation (ASCT) remains the ultimate curative option for numerous lymphoid malignancies, especially acute lymphoblastic leukemia (ALL). When relapse occurred after ASCT, prognosis is dismal especially in ALL and therapeutic options are limited (1). Donor lymphocyte infusions (DLIs) of unmanipulated allogeneic lymphocytes from the transplant donor are then commonly used.

The Role of New TKIs and Combinations with Interferon-α for the Treatment of CML

Despite the remarkable success of tyrosine kinase inhibitors (TKIs) in the treatment of CML, patients that do not respond or do not tolerate well these agents accumulate, and new options have to be found to avoid these situations. In this chapter, we discuss the importance of ponatinib, a third-generation TKI, and omacetaxine mepesuccinate, an untargeted therapy for such patients, and the use of combinations of TKI and interferon-α front line in order to prevent the onset of disease resistance.

Diagnostic and treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia

The outcome of adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has improved substantially with the introduction of tyrosine kinase inhibitors (TKIs). TKIs are now integral components of therapy for Ph+ ALL. The current consensus is that they improve patient outcomes compared with historical control patients treated with chemotherapy alone, and increase the number of patients able to receive stem cell transplant. New challenges have emerged with respect to induction of resistance mainly via Abelson tyrosine kinase mutations. Several novel kinase inhibitors with significantly more potent antileukemic activity are currently being developed. Furthermore novel immune therapies, which recruit or modify patients own T cells to fight leukemic cells, are being developed and could find an important place in Ph+ ALL therapy by few years. In this article, we reviewed treatment approaches in adults with Ph+ ALL with a focus on TKIs and combined chemotherapy regimens.