Adi Shacham-Abulafia

Has the time for first-line treatment with second generation tyrosine kinase inhibitors in patients with chronic myelogenous leukemia already come? Systematic review and meta-analysis

Second generation tyrosine kinase inhibitors have recently been introduced as first-line treatment for chronic phase chronic myelogenous leukemia. We aimed to evaluate the efficacy and safety of 2nd generation tyrosine kinase inhibitors versus imatinib as first-line treatment for these patients. We carried out a systematic review and meta-analysis of randomized controlled trials comparing 2nd generation tyrosine kinase inhibitors to imatinib as first-line treatment in chronic phase chronic myelogenous leukemia patients. Outcomes assessed were: complete cytogenetic response and major molecular response at 12, 18 and 24 months, all-cause mortality and progression to accelerated phase/blastic crisis at 12, 18 and 24 months, and chronic myelogenous leukemia related mortality and toxicity at last follow up. Relative risks were estimated and pooled using a fixed effect model. Our search yielded four trials including 2,120 patients. At 12 months, treatment with 2nd generation tyrosine kinase inhibitors significantly improved both complete cytogenetic response and major molecular response (relative risk 1.16, 95% CI: 1.09-1.23, and 1.68, 95% CI: 1.48-1.91, respectively). While major molecular response was improved at all time points, complete cytogenetic response improved at 18 months but not at 24 months. Importantly, rate of progression to accelerated phase/blastic crisis was significantly lower with the newer tyrosine kinase inhibitors throughout all time points. Second generation tyrosine kinase inhibitors improved chronic myelogenous leukemia related mortality without a statistically significant difference in all-cause mortality at 12, 18 and 24 months. We conclude that 2nd generation tyrosine kinase inhibitors can be added safely to the first-line treatment armamentarium of chronic phase chronic myelogenous leukemia patients. Although an advantage is suggested by surrogate parameters, longer follow up is necessary to see if this translates into superior overall survival.

High‐dose imatinib for newly diagnosed chronic phase chronic myeloid leukemia patients—Systematic review and meta‐analysis

Imatinib at a dose of 400 mg daily is considered frontline treatment in chronic phase chronic myeloid leukemia (CP‐CML).

Serum albumin level at diagnosis of diffuse large B-cell lymphoma: an important simple prognostic factor

This study compared the value of several simple laboratory parameters with known prognostic models for predicting survival in patients with diffuse large B‐cell lymphoma (DLBCL). The data of 157 adult patients with DLBCL diagnosed at Rabin Medical Center in 2004–2008 and treated with R‐CHOP immunochemotherapy were retrospectively reviewed. Main clinical features of the cohort were as follows: mean age 63.0 years, 43% male, 63% stage III/IV disease, 28% ECOG performance status >2, 60% elevated lactate dehydrogenase level. Median duration of follow‐up was 6.6 years. The NCCN‐International Prognostic Index (IPI) was found to be a more powerful prognosticator than the IPI. Five‐year overall survival (OS) was 69.6; 73.6% for patients with intermediate NCCN‐IPI and 38.4% for patients with poor NCCN‐IPI. On univariate analysis, pretreatment hemoglobin and albumin levels were significantly associated with survival. By albumin level, 5‐year OS was 77.6 + 4% in patients with >3.5 g/dl and 53 + 7% in patients with <3.5 g/dl (p < 0.001); 5‐year progression‐free survival (PFS) was 69.9% and 50.9%, respectively (p = 0.002). By hemoglobin level, 5‐year OS was 82.9 + 4.5% in patients with >12 g/dl and 58.8 + 5% in patients with <12 g/dl (p = 0.007); 5‐year PFS was 75.5% and 54.1%, respectively (p = 0.008). On multivariate analysis with Cox regression, pretreatment albumin level was a significant independent predictor of OS. Furthermore, 5‐year OS of patients with a high NCCN‐IPI and albumin < 3.5 g/dl was 29.2% compared with 60% in patients with albumin > 3.5 g/dl (p = 0.022). In conclusion, pretreatment albumin level is a strong prognostic factor for OS in patients with DLBCL and can discriminate high‐risk patients for good and poor prognosis. Copyright

Burkitt's lymphoma of the ovary: case report and review of the literature.

Primary Burkitt’s lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt’s lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt’s lymphoma. Characteristics predictive for the diagnosis of Burkitt’s lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.

High-Intensity Induction Chemotherapy Is Feasible for Elderly Patients with Acute Myeloid Leukemia

Background: The prognosis of elderly patients with acute myeloid leukemia (AML) is poor, and the best treatment is controversial. Since the majority of AML patients are older than 60 years, identification of those who might benefit from intensive treatment is essential. Methods: Data from electronic charts of consecutive AML patients treated in our center were analyzed. Eligibility criteria included newly diagnosed de novo or secondary AML, an age of 60 years or older, and intensive induction treatment. Results: Sixty-two patients were included in the analysis. Forty-six patients (74%) achieved complete remission (CR) after 1-2 intensive induction courses. Twenty of them received consolidation with conventional chemotherapy, 20 proceeded to allogeneic hematopoietic cell transplantation (allo-HCT), and 6 were ineligible for further treatment. The projected overall survival (OS) at 2 and 3 years was 28 and 23%, respectively. A normal karyotype, CR achievement, and allo-HCT were associated with improved OS, while an Eastern Cooperative Oncology Group performance status of 0-1 was borderline associated. The median survival and disease-free survival at 2 years was 18.7 months and 49%, respectively, for patients who underwent allo-HCT in CR1, compared to 12.8 months and 25%, respectively, for those who did not. Conclusion: Based on our data, selected eligible elderly AML patients might benefit from intensive treatment.

The Use of Myeloid Colony-Stimulating Factors in Hematologic Malignancies: The Role of Systematic Reviews and Meta-Analyses

Myeloid colony-stimulating factors (M-CSFs), which include granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), regulate the proliferation and differentiation of myeloid cells. Their use has an important role in the treatment of hematologic malignancies. Guidelines for the use of colony stimulating factors have been published by the American Society of Oncology (ASCO) in 1996 and have been updated several times, most recently in 2006. Meta-analyses of randomized controlled trials are regarded as the highest grade of evidence in clinical research and as such, compared to individual studies, they have more power in answering unresolved clinical issues. In this review, our aim is to evaluate the role of M-CSFs in hematologic malignancies based on meta-analyses conducted in the field.

Real-life Experience With Ponatinib in Chronic Myeloid Leukemia: A Multicenter Observational Study

Background: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). Patients and Methods: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. Results: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase. Only 9 patients (26%) harbored the T315I (threonine to isoleucine mutation at position 315) mutation. All patients had received ≥ 1 previous tyrosine kinase inhibitor. The median age in our cohort was 43 years (range, 9–82 years), significantly younger than expected for patients with relapsed or refractory CML and 20 years younger than the median age of patients who participated in the PACE (ponatinib Philadelphia‐positive acute lymphoblastic leukemia and CML evaluation) trial. During a median follow‐up of 14 months (range, 1–51 months), the overall response rate was 85%. Of 34 patients, 16 (47%) experienced at least a major molecular response. Of the 37 total patients, another 16 patients (43%) discontinued treatment because of disease progression (n = 6), vascular complications (n = 1), severe cytopenia (n = 2), or for other reasons (n = 7). Conclusion: In real life, ponatinib is a “niche‐drug” reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates. Micro‐Abstract In the present study, we identified 37 patients with chronic myeloid leukemia in 7 medical centers to study how ponatinib is used outside of clinical trials. At least 1 previous tyrosine kinase inhibitor had failed in all 37 patients. Their median age was 43 years (range, 9–82 years), and the overall response rate was 85%. Outside of clinical trials, ponatinib has been reserved for exceptionally young patients; however, responses can be expected even in heavily pretreated patients.