High-density lipoprotein (HDL) has an impact on myeloma outcome: Lower HDL associates with worse progression-free survival.

BACKGROUND: Multiple myeloma (MM) staging is based on beta­2 MG, albumin, LDH levels, and the presence of chromosomal abnormalities. We aimed to evaluate the impact of high-density lipoprotein (HDL) on myeloma outcomes. MATERIALS AND METHODS: This study included 148 individuals; 68 patients diagnosed with MM and 80 age, sex, comorbidity-matched controls. The relationship between HDL and myeloma stage and the association between HDL and progression-free survival (PFS) were analyzed. RESULTS: Sixty-five percent of patients were male in each group. Mean HDL level was higher in the control group than myeloma group (52.6 ± 15.02 mg/dl versus 33.79 ± 12.71) (p < 0.001). According to ISS, 39 patients (57%) had advanced stage (ISS-III) disease. To assess the optimal cut-point for HDL that makes a difference in PFS, the X­tile software program was used and in line with the created plots, the myeloma cohort was divided into two groups as HDL < 28 and ≥ 28 mg/dl. Twenty-two patients (32.4%) were in HDL < 28 group. According to the ISS, HDL < 28 group had more advanced disease than the HDL ≥ 28 group (p = 0.008). Twenty-nine patients (42.6%) progressed or died during the follow-up and 15 of these were in the HDL < 28 group. Time to progression was shorter in patients who were in the HDL < 28 group (median, 22 versus 40 months, p = 0.03). There was no statistically significant difference between these groups in terms of overall survival (p = 0.708). CONCLUSION: Myeloma patients have lower HDL than controls and HDL < 28 mg/dl associates with advanced-stage disease and shorter PFS. Therefore, HDL can be a surrogate prognostic marker in myeloma.

Myeloproliferative Neoplasms and Aspirin: Does Increased Platelet Turnover Matter?

Objective: Platelet aggregation tests and the analysis of thromboxane A2 metabolites [serum thromboxane B2 (TXB2) and urine 11-dehydro TXB2] are used to evaluate the efficacy of aspirin. In myeloproliferative neoplasms (MPNs), the immature platelet fraction (IPF) rises due to enhanced platelet turnover, and this has been thought to reduce the efficacy of aspirin. This phenomenon is overcome by the recommendation of aspirin intake in divided doses. We aimed to evaluate aspirin efficacy in patients who were receiving aspirin treatment of 100 mg/day. Materials and Methods: Thirty-eight MPN patients and 30 control patients (non-MPN patients who received a single daily dose of aspirin at 100 mg for nonhematological conditions) were enrolled. IPF, serum TXB2, and urine 11-dehydro TXB2 levels were measured and aggregation tests with arachidonic acid and adenosine diphosphate were performed by light transmission aggregometry (LTA). Results: Mean IPF and TXB2 levels were higher in the MPN group (p=0.008 and p=0.003, respectively). IPF levels were lower in patients on cytoreductive therapy in the MPN group (p=0.001), but these values were similar between patients on hydroxyurea and the non-MPN group (p=0.72). TXB2 levels did not differ according to hydroxyurea treatment status but were higher in the MPN group compared to non-MPN patients (23.63 ng/mL and 19.78 ng/mL, respectively; p=0.04). TXB2 values were higher in patients with essential thrombocythemia and a history of thrombotic events (p=0.031). No difference was observed in LTA between the MPN and non-MPN patient groups (p=0.513). Conclusion: Higher levels of IPF and TXB2 in the MPN patient group indicated platelets that could not be inhibited by aspirin. It was observed that patients under cytoreductive therapy had lower IPF values, but the expected decrease in TXB2 levels was not observed. These findings suggest that a lack of response to aspirin may be due to additional intrinsic factors rather than increased platelet turnover.

Prognostic Nutritional Index Predicts Early Mortality in Diffuse Large B-cell Lymphoma.

Objective: The international prognostic index (IPI) and the revised IPI (R-IPI) are used to determine the prognosis in diffuse large B-cell lymphoma (DLBCL). However, these scoring systems are insufficient to identify very high-risk patients. Recently, the prognostic nutritional index (PNI) -calculated with lymphocyte count and albumin- has been used to determine the prognosis in DLBCL. This study aimed to evaluate the effect of PNI score on prognosis and survival in patients with high-risk DLBCL. Methods: Patients diagnosed with DLBCL and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone were included. Pre-treatment IPI, R-IPI, and PNI scores and progression-free survival (PFS) and overall survival (OS) times were calculated. The cut-off value for PNI according to OS was determined by using the X-Tile program. Results: One hundred and ten patients were included, the median age was 63 years and the median follow-up period was 25 months. According to R-IPI, the median OS could not be reached for the very good risk group, and the median OS values were 83 and 17 months in the good and poor-risk groups, respectively (p=0.001). The cohort was divided into three groups according to the cut-off value for the PNI: patients with PNI <33 were classified as high-risk, 33-42 intermediate-risk, and ≥42 as low-risk. According to PNI, the median durations of PFS and OS were 2 months and 3 months in the high-risk group, 9 months and 19 months in the intermediate-risk group respectively, and in the low-risk group the median duration for PFS and OS could not be reached (p=0.001). Conclusions: The R-IPI is widely used to estimate the prognosis in DLBCL. But in our cohort, in the poor-risk patient group, the OS was 17 months according to R-IPI, while this period was 3 months according to PNI. This finding demonstrated that PNI might predict early mortality in DLBCL.

Are Hematologic Patients Trojan Horse for COVID-19?

Coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory distress syndrome virus (SARS-CoV-2) continues to affect people all around the world. This study aimed to compare the SARS-CoV-2 viral shedding time between patients diagnosed with hematologic diseases (HD) and a control group. A total of 110 patients were enrolled in this retrospective study; 55 patients with a diagnosis of HD and 55 sex and comorbidity matched controls without a diagnosis of HD, who caught COVID-19 at the same period. Thirty-eight patients were hospitalized in each group. Viral shedding time, COVID-19 severity, need for intensive care unit support, and mortality rates were compared between groups. Median viral shedding time was 24 days in hospitalized HD patients and 12 days in the hospitalized control group (p < 0.01) as 20 days in outpatient HD patients and 10 days in the outpatient control group (p = 0.02). Viral shedding time was longer in severe + critical COVID-19 cases in the whole cohort (median 22 days in severe + critical, and 12 days in mild + moderate) (p < 0.01). Severe + critical COVID-19 was more common in the HD group than the control group (47.2% versus 25.4%, respectively) (p = 0.017). Twenty-five patients were dead in the whole cohort. One patient was in the control group and 24 patients were in the HD group, therefore the mortality rate for the HD group was 43.6%. Because of statistically significant longer viral shedding time, longer-term isolation may be necessary for hematologic patients diagnosed with COVID-19.

A Rare Side Effect of Ibrutinib: Tumor Lysis Syndrome.

Chronic lymphocytic leukemia (CLL) is a progressive disease with an indolent course, and tumor lysis syndrome (TLS) is rarely seen in CLL. Ibrutinib is a novel bruton kinase (BTK) inhibitor increasingly used in CLL treatment. Ibrutinib has significant side effects such as atrial fibrillation, bleeding, diarrhea, and infections. However, TLS is reported rarely with ibrutinib treatment. This report focuses on a 69-year-old female patient diagnosed with relapsed CLL who developed grade 4 TLS after ibrutinib monotherapy. The patient developed TLS on the third day of ibrutinib treatment necessitating discontinuation of the treatment and initiation of hemodialysis and supportive care. Ibrutinib treatment was re-initiated at a daily dose of 140 mg therapy after an interval of seven days, and then any additional side effect was not seen. Tumor lysis syndrome secondary to ibrutinib has been reported in an increasing number of cases. There is currently no information on managing adverse effects of TLS attributed to ibrutinib. Consequently, ibrutinib treatment of this patient was not terminated, and restarted after a short interval. It must not be forgotten that TLS secondary to ibrutinib treatment may be rarely seen, and can be life-threatening. Treatment with ibrutinib should be initiated in consideration of this side effect, and the development of complication of TLS may not necessitate discontinuation of ibrutinib treatment.

The Outcomes of Chronic Myeloid Leukemia Patients With Molecular Warning Responses During Imatinib Treatment According to the European LeukemiaNet 2013 Recommendations.

BACKGROUND: In the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option. PATIENTS AND METHODS: We retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes. RESULTS: The cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment. CONCLUSION: It takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.

Third-line treatment with second-generation tyrosine kinase inhibitors (dasatinib or nilotinib) in patients with chronic myeloid leukemia after two prior TKIs: real-life data on a single center experience along with the review of the literature.

OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated. RESULTS: Out of 209 patients, third-line dasatinib/nilotinib was administered in 21. During the follow-up, 16 out of 21 patients gained and/or maintained an optimal response, and 4 patients died due to progression. Seventeen patients were alive at the time of the analysis, of which 13 were still on TKI, whereas 4 patients quit treatment. DISCUSSION: In patients failing two lines of TKI, dasatinib or nilotinib can be beneficial and safely administered as a third-line treatment especially in nations with restricted resources.