Retrospective evaluation of lumbar puncture and intrathecal chemotherapy in thrombocytopenic patients.

INTRODUCTION: Lumbar puncture (LP) and intrathecal chemotherapy (IT CT) are common procedures and treatment options for hematologic patients. Although they can also be used in thrombocytopenic patients, there is no consensus on the safe cutoff value of platelet counts for LP and IT CT practices. AIM: This research aimed to determine the safety of LP and IT CT administration in thrombocytopenic patients using different cutoff platelet values. METHODS: One hundred and fifty-two adult patients who had LP indications were evaluated. Among them, 42 patients received IT CT. The cerebrospinal fluid results from 100 procedures were available. RESULTS: The preprocedural platelet count was <100.000/mm3 and <50.000/mm3 in 41 (41 %) and 18 (18 %) patients, respectively. Ten of these patients received platelet transfusion prior to LP. In the untransfused group, the platelet count was <50.000/mm3 in 12 (12 %) patients, among whom seven patients had a platelet count of <30.000/mm3. The traumatic tap was comparable among the transfused and untransfused groups (p = 0.632). No correlation was observed between the thrombocyte value and the traumatic tap (p = 0.891). The ratio of the traumatic tap was not significant between the patient groups with a platelet count of ≥50.000/mm3 or <50.000/mm3 (p = 0.418). After adding the transfused patients, the traumatic tap ratio remained nonsignificant between the two groups (p = 0.851). CONCLUSION: Hemorrhagic complications were rare in the thrombocytopenic patients who received IT CT after the LP procedure applied by experienced specialists. However, further prospective large studies evaluating the safety of procedures in thrombocytopenic patients are needed to make clear conclusion.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Synthetic marijuana "K2" induced ITP.

Immune thrombocytopenia (ITP) is a heterogeneous disease which can be primary or secondary due to other conditions such as drugs. CB2 receptors (CB2R) also have a role in the ITP pathogenesis as CB2 receptor gene (CNR2) polymorphisms are associated with chronic immune thrombocytopenia and autoimmune diseases. K2 is synthetic marijuana which acts on cannabinoid receptors that are found on immune cells and thrombocytes. Here, we present a case who presented with ITP secondary to K2 usage and was successfully treated with 1 mg/kg prednisolone. This is the first ITP case in the literature due to K2. It is important in the era of the new drugs development of the CB2R mimetics.

Comparison of two minimal invasive techniques of splenectomy: Standard laparoscopy versus transumbilical multiport single-site laparoscopy with conventional instruments.

BACKGROUND: Laparoendoscopic single-site (LESS) splenectomy which is performed on small number of patients, has been introduced with better cosmetic outcome, less postoperative pain, greater patient satisfaction and faster recovery compared to standard laparoscopy. MATERIALS AND METHODS: Thirty six patients were included in the study comparing standard laparoscopic splenectomy (LS, 17 patients) transumbilical multiport splenectomy performed with conventional laparoscopic instruments (TUMP-LS, 19 patients). Two groups of patients were compared retrospectively by means of operation time, intra- and postoperative blood loss, perioperative complications, packed red cell and platelet requirements, lenght of hospitalization, pain scores and patient satisfaction. RESULTS: There was no mortality in any of the groups, and no significant differences determined in operative time (P = 0,069), intraoperative blood loss (P = 0,641), patient satisfaction (P = 0,506), pain scores (P = 0,173) and the average length of hospital stay (P = 0,257). Umbilical incisions healed uneventfully and no hernia formation or wound infection was observed during follow-up period (2-34 months). There were no conversions to open surgery. CONCLUSIONS: Transumbilical multiport splenectomy performed with the conventional laparoscopic instruments is feasible and could be a logical alternative to classical laparoscopic splenectomy by combining the advantages of single access techniques and standard laparoscopy.

The clinical features, treatment and prognosis of neutropenic fever and Coronavirus disease 2019 results of the multicentre teos study.

This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity. Study period was 15 March 2020-15 August 2021. A total of 170 cases (58 female, aged 59 ± 15.5 years) that fulfilled the inclusion criteria were included in the study. One-month mortality rate (OMM) was 44.8%. The logistic regression analysis showed the following significant variables for the mentioned dependent variables: (i) achieving PCR negativity: receiving a maximum of 5 days of favipiravir (p = 0.005, OR 5.166, 95% CI 1.639-16.280); (ii) need for ICU: receiving glycopeptide therapy at any time during the COVID-19/FEN episode (p = 0.001, OR 6.566, 95% CI 2.137-20.172), the need for mechanical ventilation (p < 0.001, OR 62.042, 95% CI 9.528-404.011); (iii) need for mechanical ventilation: failure to recover from neutropenia (p < 0.001, OR 17.869, 95% CI 3.592-88.907), receiving tocilizumab therapy (p = 0.028, OR 32.227, 95% CI 1.469-707.053), septic shock (p = 0.001, OR 15.4 96% CI 3.164-75.897), and the need for ICU (p < 0.001, OR 91.818, 95% CI 15.360-548.873), (iv) OMM: [mechanical ventilation (p = 0.001, OR 19.041, 95% CI 3.229-112.286) and septic shock (p = 0.010, OR 5.589,95% CI 1.509-20.700)]. Although it includes a relatively limited number of patients, our findings suggest that COVID-19 and FEN are associated with significant mortality and morbidity.

Sticky platelet syndrome in patients with uninduced venous thrombosis.

OBJECTIVE: Sticky platelet syndrome (SPS) is a common autosomal dominant inherited platelet disorder. SPS is characterized by platelet hyperreactivity and is associated with arterial and venous thrombosis. The aim of this study was to determine the role of SPS in patients with uninduced venous thrombosis. MATERIAL AND METHODS: The study included 28 patients (15 male and 13 female) with uninduced venous thrombosis. SPS was defined according to Mammen's aggregation method, which is described in detail elsewhere. RESULTS: According to the defined ranges for platelet hyperreactivity, 3 (50%) patients, 2 (33%), and 1 (17%) (n =6 [21%]) with a confirmed diagnosis were classified as type II, I, and III SPS, respectively. In 1 patient SPS was the only hereditary abnormality noted. The other 5 patients carried other inherited coagulation defects, in addition to SPS. CONCLUSION: The present findings indicate that the prevalence of SPS was 21% in the patients with uninduced venous thrombosis. We therefore suggest that SPS should be considered in the differential diagnosis of such cases. CONFLICT OF INTEREST: None declared.

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.

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.

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.

Transcriptomic analysis of asymptomatic and symptomatic severe Turkish patients in SARS-CoV-2 infection.

Objective: Coronavirus disease 2019 (COVID-19), leading to mild infection (MI), acute respiratory distress syndrome or death in different persons. Although the basis of these variabilities has not been fully elucidated, some possible findings have been encountered. In the present study, we aimed to reveal genes with different expression profiles by next-generation sequencing of RNA isolated from blood taken from infected patients to reveal molecular causes of different response. Methods: Two healthy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative control individuals (NCI), two SARS-CoV-2-positive patients who have MI, and two patients who have critical infection (CI) were included in the study. Total RNA was extracted from blood samples and sequenced. Raw RNA-Seq data were analyzed on Galaxy platform for the identification of differentially expressed genes and their pathway involvements. Results: We found that 199 and 521 genes were downregulated in whole blood of COVID-19-positive CI patients compared to NCI and MI patients, respectively. We identified 21 gene ontology pathways commonly downregulated in CI patients compared to both NCI and MI, mostly associated with innate and adaptive immune responses. Three hundred and fifty-four and 600 genes were found to be upregulated compared to NCI and MI, respectively. Upregulated six pathways included genes that function in inflammatory response and inflammatory cytokine release. Conclusion: The transcriptional profile of CI patients deviates more significantly from that of MI in terms of the number of differentially expressed genes, implying that genotypic differences may account for the severity of SARS-CoV-2 infection and inflammatory responses through differential regulation of gene expression. Therefore, further studies that involve whole genome analysis coupled with differential expression analysis are required in order to determine the dynamics of genotype - gene expression profile associations.

Impact of COVID-19 on Outcomes of Patients with Hematologic Malignancies: A Multicenter, Retrospective Study.

Objectives: Patients with hematological malignancies have a high risk of mortality from coronavirus disease 2019 (COVID-19). This study aimed to investigate the impact of COVID-19 on mortality rates in patients with various hematological malignancies and to determine risk factors associated with all-cause mortality. Methods: A multicenter, observational retrospective analysis of patients with hematological malignancies infected with COVID-19 between July 2020 and December 2021 was performed. Demographic data, clinical characteristics, and laboratory parameters were recorded. Patients were grouped as non-survivors and survivors. All-cause mortality was the primary outcome of the study. Results: There were 569 patients with a median age of 59 years. Non-Hodgkin lymphoma (22.0%) and multiple myelomas (18.1%) were the two most frequent hematological malignancies. The all-cause mortality rate was 29.3%. The highest mortality rates were seen in patients with acute myeloid leukemia (44.3%), acute lymphoid leukemia (40.5%), and non-Hodgkin lymphoma (36.8%). The non-survivors were significantly older (p<0.001) and had more comorbidities (p<0.05). In addition, there were significantly more patients with low lymphocyte percentage (p<0.001), thrombocytopenia (p<0.001), and high CRP (p<0.001) in the non-survived patients. Age ≥ 65years (p=0.017), cardiac comorbidities (p=0.041), and continuation of ongoing active therapy for hematological cancer (p<0.001) were the independent risk factors for the prediction of mortality. Conclusions: In patients with hematological malignancies, coexistent COVID-19 leads to a higher mortality rate in elderly patients with more comorbidities. Acute myeloid and lymphoid leukemia and non-Hodgkin lymphoma have the highest mortality rates. Older age, cardiac diseases, and continuation of ongoing active therapy for hematological cancer are the independent risk factors for mortality in hematological malignancy patients with COVID-19.

Real-Life Experience Regarding Clinical Characteristics and Treatment Outcome in Non-Cutaneous Peripheral T-Cell Lymphomas: A Multicenter Study of the Turkish Hematology Research and Education Group (ThREG)

Objective: Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL. Materials and Methods: We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016. Results: Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and event-free survival rates were significantly different between the transplant and non-transplant groups (p<0.01, and p=0.033, respectively). Conclusion: The retrospective analysis of a large volume of real-life data on the Turkish experience regarding non-cutaneous PTCL patients showed consistent results compared to other unselected PTCL cohorts with some minor differences in terms of survival and transplantation outcomes. The long-term outcome of patients who receive autologous hematopoietic cell transplantation as part of upfront consolidation or salvage therapy is favorable compared to patients who are unable to receive high-dose therapy.

The Relationship Between Hematological Malignancy and Lipid Profile.

OBJECTIVE: Hypocholesterolemia is a metabolism disorder that may be seen in chronic diseases and malignancies. Various dyslipidemia profiles have been shown in adult and pediatric hematological malignancies. We aimed to evaluate the lipid profile properties in patients diagnosed with a hematological malignancy compared to a healthy control group. METHOD: Out of 1213 patients diagnosed with hematologic malignancy, the data of 98 patients whose pretreatment lipid profiles had already been studied, were reviewed. Forty healthy individuals were selected as the control group. The levels of total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were compared. RESULTS: Triglyceride values were significantly higher (p=0.02), and the total cholesterol, LDL and HDL levels were lower in the study group compared to the control group. Triglyceride values were higher (p=0.013), and HDL levels were lower (p=0.022) in parallel with increases in uric acid levels. There was a significant correlation between the International Prognostic Index (IPI) score and TG (p=0.003) in those diagnosed with non-Hodgkin lymphoma (NHL). Whereas no significant correlation was found between TG, total cholesterol, and LDL values in the limited (early) and advanced stage NHL, while a significant negative correlation was found with HDL (p=0.027). CONCLUSION: Hypertriglyceridemia, as well as low LDL and HDL values may be seen in hematological malignancies. It should be kept in mind that there may be chronic diseases and malignancies in the etiology of incidental hypocholesterolemia and hypertriglyceridemia. Further studies are needed on this subject to determine the effects of dyslipidemia on the pathogenesis and prognosis of the disease in hematological malignancies.

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.

Lung transplantation for graft-versus-host disease after allogeneic stem cell transplantation: A report of two cases.

Allogeneic peripheral stem cell transplantation is an effective treatment of malignant and non-malignant hematological diseases. However, it is associated with several complications, such as graft-versus-host disease, and also various complications involving different organ systems. Late-onset non-infectious lung complication is one of them. This pathology may also affect the different anatomical regions in the lung as parenchymas, bronchi, or vessels and may manifest with different clinical presentations. Lung transplantation can be an effective treatment in patients with pulmonary complications after allogeneic stem cell transplantation and also in patients who do not respond to treatment adequately and with a limited life expectancy. Herein, we report two rare cases who underwent lung transplantation after allogeneic stem cell transplantation.

The role of atopy in the pathogenesis of bleomycin pulmonary toxicity.

INTRODUCTION: Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT. METHODS: We assessed retrospectively our cohort of patients with Hodgkin Lymphoma treated with bleomycin between 2014 and 2016 for their demographic, clinical features, including BPT development, atopy status and risk factors for BPT. Then they were invited for allergy testing and blood sample collection. The samples were stimulated with different stimuli (Bleomycin, IL-33, TSLP) for 24 h on cell culture. The culture supernatants were analysed for TGF-ß, Galectin3, Arginin, Amphiregulin, Eotaxin, IFNγ, TNFα, IL1ß, 4, 5, 6, 10, 13, 17, MIP-1α, and bleomycin hydrolase (BLH) levels. RESULTS: The cohort consisted of 51 patients showed that atopy was the only significant risk factor for BPT occurrence (OR: 7.2, p = 0.007). Fourteen subjects were included for blood analysis. The analysis of supernatants at the unstimulated condition revealed that BLH and Amphiregulin were significantly lower in patients who had BPT than controls. The BLH cut-off that best identified a history of BPT was 175.31 (Sensitivity: 62.5%, specificity: 100%). Following the stimulation, BLH reduced compared to the unstimulated condition and the difference between groups remained significant (p < 0.05). CONCLUSION: Our study is the first to report that low levels of bleomycin hydrolase in allergic individuals may be predisposing to a possible pathway of fibrosis.