GDF11 level and its effect on prognosis in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the proliferation of CD34 positive self-renewing malignant hematopoietic stem cells. Previous studies have shown that the transforming growth factor beta (TGFß) pathway plays a role in AML pathogenesis, especially by affecting the microenvironment. Growth differentiation factor 11 (GDF11) is a member of the TGFß superfamily, involved in embryological development and known as rejuvenating factor. In this study, our aim was to determine the serum GDF11 level in patients with AML, to compare it with the control group, to determine its relationship with follistatin, vimentin, and E-cadherin levels, and to determine whether GDF11 influences AML prognosis. Serum GDF11, vimentin, follistatin, and E-cadherin levels of newly diagnosed or relapsed/refractory AML patients and age- and gender-matched control group were measured by enzyme-linked immunosorbent assay. Serum GDF11 level was higher in the patient group (263.87 ± 126.54 ng/L) compared to the control group (211.54 ± 61.47 ng/L; p = 0.035). GDF11 level did not change according to age, gender, hemoglobin level, and bone marrow blast rate. No correlation was found between GDF11 level, response rates, and survival status of the patients. A positive correlation was detected between GDF11, E-cadherin, and vimentin levels. As a conclusion, increased serum GDF11 levels in AML patients may be linked to the regeneration ability of leukemic stem cells. There is a need for studies investigating GDF11 expression in myeloblasts.

Adult acute megakaryoblastic leukemia with persistent diarrhea and extreme thrombocytosis: A very unusual case.

ABSTRACT: Acute megakaryoblastic leukemia (AML-M7) is rarely seen in adult patients and patients usually present with cytopenias. Here we discuss diagnostic challenges and pathologic features in a patient with AML-M7 who presented with thrombocytosis and diarrhea. A 63-year-old male patient presented with persistent diarrhea lasting for 2 months, fatigue, and thrombocytosis. The diagnostic workup included a stool analysis, endoscopy colonoscopy, and imaging studies; however, these studies did not reveal any possible etiology. The hematologic evaluation included peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry, and cytogenetic analysis. Eventually, according to pathologic and flow cytometric findings, a diagnosis of AML-M7 was made. Diagnosis of AML-M7 may be challenging, especially in adult patients with atypical presentation. Patients with megakaryoblastic leukemia respond poorly to standard induction regimens and they should be advised to participate in a clinical trial.

Bosutinib-induced massive pleural effusion: Cross-intolerance with all tyrosine kinase inhibitors.

BACKGROUND: The discovery of tyrosine kinase inhibitors provided a breakthrough in the treatment of chronic myeloid leukemia. Nowadays, the management of tyrosine kinase inhibitor-related side effects is one of the important problems in chronic myeloid leukemia treatment. Grades 3-4 pulmonary toxicity; especially pleural effusion is mostly seen with dasatinib treatment but rarely seen with nilotinib and bosutinib. Development of cross-intolerance due to pleural effusion is not an expected situation. Pleural effusion related to tyrosine kinase inhibitors is mostly exudative in nature with abundant lymphocytes. CASE REPORT: Massive pleural effusion developed in a 59-year-old male patient with chronic myeloid leukemia, who was being treated with bosutinib. In the past, the patient had experienced massive pleural effusion also with dasatinib and nilotinib. The evaluation for differential diagnosis of pleural effusion did not reveal any additional malignancy. MANAGEMENT AND OUTCOME: After discontinuation of bosutinib and initiation of prednisolone, pleural effusion was totally resolved. Prednisolone was gradually discontinued and third-generation tyrosine kinase inhibitor ponatinib was started. After 12 months of follow-up, massive pleural effusion occurred again, leading to discontinuation of ponatinib. DISCUSSION: Cross-intolerance is an important problem in the tyrosine kinase inhibitor era. The significance of this case is the development of cross-intolerance to all second-generation tyrosine kinase inhibitors and furthermore to a third-generation tyrosine kinase inhibitor. Management strategies for pleural effusion and close follow-up are important.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.

Iron deficiency anemia (IDA) is a major public health problem especially in underdeveloped and developing countries. Zinc is the co-factor of several enzymes and plays a role in iron metabolism, so zinc deficiency is associated with IDA. In this study, it was aimed to investigate the relationship of symptoms of IDA and zinc deficiency in adult IDA patients. The study included 43 IDA patients and 43 healthy control subjects. All patients were asked to provide a detailed history and were subjected to a physical examination. The hematological parameters evaluated included hemoglobin (Hb); hematocrit (Ht); red blood cell (erythrocyte) count (RBC); and red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (МСН), mean corpuscular hemoglobin concentration (МСНС), and red cell distribution width (RDW). Anemia was defined according to the criteria defined by the World Health Organization (WHO). Serum zinc levels were measured in the flame unit of atomic absorption spectrophotometer. Symptoms attributed to iron deficiency or depletion, defined as fatigue, cardiopulmonary symptoms, mental manifestations, epithelial manifestations, and neuromuscular symptoms, were also recorded and categorized. Serum zinc levels were lower in anemic patients (103.51 ± 34.64 µ/dL) than in the control subjects (256.92 ± 88.54 µ/dL; <0.001). Patients with zinc level <99 µ/dL had significantly more frequent mental manifestations (p < 0.001), cardiopulmonary symptoms (p = 0.004), restless leg syndrome (p = 0.016), and epithelial manifestations (p < 0.001) than patients with zinc level > 100 µ/dL. When the serum zinc level was compared with pica, no statistically significant correlation was found (p = 0.742). Zinc is a trace element that functions in several processes in the body, and zinc deficiency aggravates IDA symptoms. Measurement of zinc levels and supplementation if necessary should be considered for IDA patients.