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The standard therapies for polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome are radiation therapy, high-dose chemotherapy followed by autologous stem cell transplantation, and lenalidomide combined with dexamethasone. Daratumumab was reported to be effective for treatment-naive and relapsed POEMS syndrome, but treatment options for relapsed POEMS syndrome with poor prognostic factors or cytogenetic abnormalities have not been established due to a lack of studies in these patients. Here, we describe a case of relapsed POEMS syndrome with bone plasmacytoma harboring a newly detected 17p deletion after high-dose chemotherapy followed by autologous stem cell transplantation and radiation therapy in a male patient. He was successfully treated with daratumumab plus lenalidomide and dexamethasone (Dara-Rd). Dara-Rd could be effective in relapsed POEMS syndrome with 17p deletion, which is known as a poor cytogenetic abnormality in multiple myeloma. This report may broaden the application of Dara-Rd for POEMS syndrome. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are a clonal hematopoietic stem cell (HSC) disorders. Cytogenetics plays a vital role in pathogenesis, diagnosis, prognosis, and determining treatments in MDS. Cytogenetic studies on CD 34 cells in Asian MDS patients are limited. The aim of conducting this study was to compare the karyotypic features of CD 34 cells and their bone marrow (BM) karyotypes. BM samples of 20 primary MDS patients were collected. BM-CD 34 cells were isolated by CD34 positive selection. Conventional karyotyping was performed on primary BM samples and isolated CD 34 cells. Fluorescence in situ hybridization (FISH) was performed to confirm del(5q) by using XL 5q31/5q33 locus-specific probe. Chromosomal abnormalities were detected in 41 % (7/17) of BM and 40 % (8/20) of HSC karyotypes. BM and HSC karyotypes were similar (94 %) except in one (BM-normal; CD 34+ cells had del(5q)) where the patient showed characteristic del(5q) phenotype. The abnormalities found were del(5q)-10 % (2/20), del(11q)-5 % (1/20), del(12p)-5 % (1/20), 47,XY,+19-5 % (1/20), hypodiploidy-5 % (1/20), and random loss of chromosomes-10 % (2/20). The percentage of abnormal metaphases counted per case was higher for CD 34 cell cultures than for BM cultures. Culture failure were less for CD 34 cells when compared to BM. Sample limitation for BM does not apply for CD 34 cells if cultures can be maintained. Although the abnormal karyotypes counted were greater using CD 34 cells than BM, there was no statistically significant difference ( p > 0.05). Detection of karyotypic abnormalities could be greater when using CD 34 cells. All the karyotypic abnormalities reported in this study had been previously known in MDS. Further large scale studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]

Backgrounds: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by a clonal accumulation of mature apoptosis-resistant neoplastic cells. It is also a heterogeneous disease with a variable clinical outcome. Here, we present a review of currently known (epi)genetic alterations that are related to the etiology, progression and chemo-refractoriness of CLL. Relevant literature was identified through a PubMed search (1994-2014) of English-language papers using the terms CLL, signaling pathway, cytogenetic abnormality, somatic mutation, epigenetic alteration and micro-RNA. Results: CLL is characterized by the presence of gross chromosomal abnormalities, epigenetic alterations, micro-RNA expression alterations, immunoglobulin heavy chain gene mutations and other genetic lesions. The expression of unmutated immunoglobulin heavy chain variable region (IGHV) genes, ZAP-70 and CD38 proteins, the occurrence of chromosomal abnormalities such as 17p and 11q deletions and mutations of the NOTCH1, SF3B1 and BIRC3 genes have been associated with a poor prognosis. In addition, mutations in tumor suppressor genes, such as TP53 and ATM, have been associated with refractoriness to conventional chemotherapeutic agents. Micro-RNA expression alterations and aberrant methylation patterns in genes that are specifically deregulated in CLL, including the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and linked to distinct clinical parameters. Conclusions: Specific chromosomal abnormalities and gene mutations may serve as diagnostic and prognostic indicators for disease progression and survival. The identification of these anomalies by state-of-the-art molecular (cyto)genetic techniques such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), single nucleotide polymorphism (SNP) microarray-based genomic profiling and next-generation sequencing (NGS) can be of paramount help for the clinical management of these patients, including optimal treatment design. The efficacy of novel therapeutics should to be tested according to the presence of these molecular lesions in CLL patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the characteristics and outcome in a group of pediatric patients with hematological malignancies who developed hemophagocytosis at diagnosis or during the disease course. Eight patients with hematological malignancy and associated hemophagocytosis were included. The initial diagnosis was juvenile myelomonocytic leukemia (JMML) in five, nonlymphoblastic leukemia (ANLL) in two, and T-cell lymphoma associated with myeloproliferative syndrome in one patient. Hemophagocytosis was concomitantly present at the time of diagnosis of the primary disease in four of the five patients with JMML and in the two patients with ANLL. Three had abnormalities related to chromosome 8 [(trisomy 8, monosomy 8, and t (8;13) (p11; p12)], and one had inversion 16. Multiple chromosomal losses were present in one patient, including both chromosomes 8 and 16. Bone marrow karyotyping revealed 46, XX; 47, XXX mosaicism in one patient. Two patients had PTPN11 mutation and one patient k-RAS mutation. The patients with JMML and neurofibromatosis ( n = 2), the patient with lymphoma and t (8;13) positive AML, and a fourth patient with PTPN11 mutation did not remit and had unfavorable outcomes. [ABSTRACT FROM AUTHOR]

Purpose To find the frequency and types of major chromosomal abnormalities with nonobstructive azoospermia and severe oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in Isparta (South of Turkey), and to investigate the general characteristics in this infertile male population. Methods and patients A total of 115 infertile males (92 were azoospermic, 23 severe oligospermic) were studied for the cytogenetic evaluation prior to use of assisted reproduction techniques. Also, 60 fertile males as a control group were studied. Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Levels of luteinising hormone, follicle-stimulating hormone (FSH), testosterone and prolactin were obtained and a testicular sonography examination was conducted. Results The total prevalence of chromosomal abnormalities was found to be 4.3% (5/115), including 4 patients with Klinefelter's Syndrome and 1 patient with gonadal dysygenesis (46XX). All of them were azoospermic males, corresponding to a frequency of 5.4%(5/92 patients). Oligozoospermic males and control males had no chromosomal abnormalities. There was a significant difference in serum FSH, LH, mean testicular volume and smoking when comparing patients (both azoospermic and oligozoospermic) and control groups (p<0.05). Also, there was a significant difference in serum FSH, LH and mean testicular volume when compared with azoospermic and oligozoospermic patients (p<0.05) Conclusions The occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques. [ABSTRACT FROM AUTHOR]

Cytogenetic abnormalities in patients with essential thrombocythemia (ET) are infrequent. Their role in survival of patients and disease transformation is not extensively studied. We describe cytogenetic abnormalities in 172 patients with ET at a single institution. At presentation nine (5.2%) patients had cytogenetic abnormality and three (1.7%) additional patients acquired them during follow-up. Survival of patients with cytogenetic changes at presentation did not differ when compared to the patients with normal karyotype. The more common were abnormalities of chromosome 9 (n = 4), 20 (n = 2), 5 (n = 2), and complex abnormalities (n = 2). Forty-one patients (23.8%) had additional cytogenetic tests performed for monitoring purposes during follow-up. Five patients (2.9%) with normal karyotype transformed to myelofibrosis (MF) without developing new cytogenetic changes at transformation. Two patients (1.2%) with normal karyotypes at presentation transformed to myelodysplastic syndrome and acute myeloid leukemia, respectively. Both acquired complex cytogenetic changes at the time of transformation. There is no rationale for repeating cytogenetic tests in ET patients on follow up, unless blood cell count changes suggest possible transformation. [ABSTRACT FROM AUTHOR]

Opinion Statement: Acute myeloid leukemia (AML) patients with a complex karyotype (CK-AML) show at least 3 unrelated clonal cytogenetic abnormalities with notoriously poor outcome. Such cases fall into either AML with myelodysplasia-related changes or therapy-related AML in the current World Health Organization classification of AML. Allogeneic stem cell transplantation is one of the only treatment modalities that can provide a long-term survival benefit and is recommended as a consolidative treatment in patients who are able to achieve complete remission. Unfortunately, transplantation is also associated with a higher relapse rate and more than half of CK-AML patients relapse from disease within the first 2 years. The probability of achieving remission with traditional induction using cytarabine and daunorubicin or idarubicin ("7 + 3") is so small that investigational therapies should be considered up front in these patients. Less intensive therapeutic backbones, typically using one of the hypomethylating agents, azacitidine or decitabine, minimize toxicity and show a trend toward the improved overall survival. CPX 351 (Vyxeos) is a liposomal formulation of cytarabine and daunorubicin and this encapsulation leads to prolonged exposure to the two drugs. This drug is approved for AML patients with MDS-related changes and therapy-related AML, both of which are frequently associated with complex karyotype. Such patients show improved outcome in trials using this combination. Combination therapy that includes venetoclax (BCL2 inhibitor) with hypomethylating agents may also be appropriate for such patients. [ABSTRACT FROM AUTHOR]