Unmet clinical needs and challenges in the management of acute leukemia in Turkey: a modified Delphi study.

Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient-physician communication in acute leukemia (AL). Materials & methods: The study was based on a modified Delphi approach. A questionnaire including the major potential obstacles was circulated twice among 13 hematologists. Results: The obstacles in AL management were limited access to the novel treatments and genetic tests, limited bed capacity, insufficient level of knowledge among allied health personnel, limited availability of psycho-oncological support and low levels of awareness in the population about the importance of stem cell donation. Conclusion: The challenges in the management of AL are critical to guide the efforts to improve the quality of healthcare delivery and the evidence-based decision making at treatment of AL patients.

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data.

Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

The effect of haemoglobin, albumin, lymphocyte and platelet score on the prognosis in patients with multiple myeloma.

INTRODUCTION: In multiple myeloma cases, a variety of prognostic parameters have been identified, which contain the Durie-Salmon classification and the international staging system (ISS) that takes the serum ß2 microglobulin and albumin levels, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). This study investigates the effect of haemoglobin, albumin, lymphocyte and platelet (HALP) score which is a marker of inflammation status and nutrition, at the time of diagnosis for the patients with multiple myeloma on prognosis. METHODS: A total of 200 multiple myeloma patients with HALP scores calculated from serum haemoglobin, albumin, lymphocyte count and platelet levels at the time of diagnosis were retrospectively examined. The effect of HALP score on overall survival (OS) and progression-free survival and its relationship between the previously evaluated prognostic parameters were investigated. RESULTS: The optimal cut-off value with the ROC curves for the HALP score was 28.8. The patients were divided into two groups according to the optimal value of the HALP score (low-score group: HALP ≤28.8 [n: 134] and high-score group HALP >28.8 [n: 66]). In the group with the high HALP score, the OS was statistically longer than the low HALP score group (84 months and 53 months; p = 0.0001). In addition, when the effects of NLR, PLR, HALP score and ISS stage on OS were examined by multivariate analysis, all these markers were found to be statistically significant predictors. CONCLUSIONS: HALP score may be a valuable prognostic marker for patients with multiple myeloma.

Whole Transcriptome Sequencing Reveals Cancer-Related, Prognostically Significant Transcripts and Tumor-Infiltrating Immunocytes in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) subtype characterized by overexpression of CCND1 and SOX11 genes. It is generally associated with clinically poor outcomes despite recent improvements in therapeutic approaches. The genes associated with the development and prognosis of MCL are still largely unknown. Through whole transcriptome sequencing (WTS), we identified mRNAs, lncRNAs, and alternative transcripts differentially expressed in MCL cases compared with reactive tonsil B-cell subsets. CCND1, VCAM1, and VWF mRNAs, as well as MIR100HG and ROR1-AS1 lncRNAs, were among the top 10 most significantly overexpressed, oncogenesis-related transcripts. Survival analyses with each of the top upregulated transcripts showed that MCL cases with high expression of VWF mRNA and low expression of FTX lncRNA were associated with poor overall survival. Similarly, high expression of MSTRG.153013.3, an overexpressed alternative transcript, was associated with shortened MCL survival. Known tumor suppressor candidates (e.g., PI3KIP1, UBXN) were significantly downregulated in MCL cases. Top differentially expressed protein-coding genes were enriched in signaling pathways related to invasion and metastasis. Survival analyses based on the abundance of tumor-infiltrating immunocytes estimated with CIBERSORTx showed that high ratios of CD8+ T-cells or resting NK cells and low ratios of eosinophils are associated with poor overall survival in diagnostic MCL cases. Integrative analysis of tumor-infiltrating CD8+ T-cell abundance and overexpressed oncogene candidates showed that MCL cases with high ratio CD8+ T-cells and low expression of FTX or PCA3 can potentially predict high-risk MCL patients. WTS results were cross-validated with qRT-PCR of selected transcripts as well as linear correlation analyses. In conclusion, expression levels of oncogenesis-associated transcripts and/or the ratios of microenvironmental immunocytes in MCL tumors may be used to improve prognostication, thereby leading to better patient management and outcomes.

Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosis.

Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.

Therapeutic plasma exchange in neurological diseases: Eleven years experience at a tertiary care center in Turkey.

Therapeutic plasma exchange (TPE) is an apheresis procedure in which plasma is separated from the blood cellular components ex vivo, allocated, and replaced with another plasma or a plasma-replacing fluid. This study aimed to define the rate of complications and determine TPE distribution in various neurological diseases. Our study is a retrospective analysis of neurologic diseases requiring TPE between 2008 and 2019 that were selected using the medical records of neurology departments and apheresis units database. We performed 1459 TPE procedures on 207 patients between 2008 and 2019. TPE Procedure is most frequently applied in patients with Myasthenia-Gravis syndrome (34.7%). The complication ratio was 1.6% from a total of 1459 TPE procedures. The most commonly specified adverse event was allergic reactions 11 (5.3%), followed by hypotension 6 (2.9%). TPE was safe and tolerable, with manageable complications in experienced hands.

Assessment of Bone Marrow Biopsy and Cytogenetic Findings in Patients with Multiple Myeloma

Objective: Multiple myeloma (MM) is a malignant condition characterized by the accumulation of malignant plasma cells. Although MM remains incurable, the survival of MM patients has improved considerably due to the application of autologous stem cell transplantation, novel agents, and advanced treatment strategies. This study aimed to determine the cytogenetic characterization and bone marrow (BM) features of Turkish patients with MM. Materials and Methods: Eighty-five MM patients were admitted to Dokuz Eylül University Hospital in Turkey. BM samples of these MM patients were subjected to cytogenetic analyses at diagnosis and during therapy as a part of therapeutical and clinical evaluation. A complete cytogenetic study was performed using the G-banding technique. Fluorescence in situ hybridization (FISH) analysis was performed using cytoplasmic immunoglobulin. The degree of BM fibrosis was determined using reticulin histochemical staining. We determined the percentage of BM plasma cells based on the extent of CD38 staining. Results: Eighty-five MM patients were retrospectively identified between 2015 and 2021. The median age was 63 (38-90) years. Of the 85 patients, 60 (70.6%) were male and 25 (29.4%) were female. Seventy-two (84.7%) cases had BM fibrosis at the time of diagnosis. The most common was grade 2 fibrosis, recorded in 35 cases (41.2%). About 72.9% of the patients showed more than 50% plasma cells. FISH analysis indicated the presence of abnormal chromosomes in 37% (32/85) of the patients. The most frequent abnormality was Immunoglobulin heavy-chain (IGH) translocation (21.3%). Conclusion: Subgroup analysis of IGH mutations is crucial in the identification of high-risk MM patients. We believe that our study will contribute to the determination of BM biopsy and cytogenetic features of MM patients in our country.

Evaluation of using fresh frozen plasma for patients with cirrhosis at a tertiary healthcare center in Turkey: Strict transfusion policies are essential.

AIM: Management of blood transfusions is a critical issue, especially in cirrhotic patients, because of the absence of national policies in many countries. Fresh frozen plasma (FFP) is a common blood component misused excessively in various clinical situations and cirrhosis patients without any scientific rationale. We evaluated the FFP transfusions in patients with cirrhosis at our tertiary care hospital. MATERIAL AND METHOD: The cases with cirrhosis diagnosed between 2014 and 2020 were selected using the hospital database. The appropriateness of FFP transfusion was determined based on the Practice Guidance by the American Association for the Study of Liver Diseases and Italian guidelines. RESULT: Two hundred and six liver cirrhosis patients were identified who received FFP transfusion. The median age was 63 (22-94). Of the 206 patients, 79 (38.3 %) were female, and 127 (61.7 %) were men. The most common causes of liver cirrhosis were alcohol (27.7 %). 45.6 % of the patients were in Child-Pugh Class C. We found 62.1 % of FFP replacements were inappropriately used. Most inappropriate use of FFP (22.8 %, n = 47) occurred to correct prolonged INR in the absence of bleeding. CONCLUSION: To avoid inappropriate usage of FFP, regular utilization reviews and formal education programs can be helpful. Our clinic has planned to arrange educational programs for physicians to use blood products appropriately and minimize transfusion-related side effects.

A Real-life Turkish Experience of Venetoclax Treatment in High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia.

INTRODUCTION: Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in combination with either low-dose cytarabine (ARA-C) or hypomethylating agents. We aimed to collect and share data among the efficacy and safety of venetoclax both as a monotherapy or in combination with other drugs used to treat high-risk MDS or AML. MATERIALS AND METHODS: A total of 60 patients with a median age of 67 (30-83) years from 14 different centers were included in the final analysis. Thirty (50%) of the patients were women; 6 (10%) of the 60 patients were diagnosed with high-risk MDS and the remaining were diagnosed with AML. RESULTS: The best objective response rate (complete remission [CR], complete remission with incomplete hematological recovery (CRi), morphological leukemia-free state [MLFS], partial response [PR]) was 35% in the entire cohort. Best responses achieved during venetoclax per patient number were as follows: 7 CR, 1 CRi, 8 MLFS, 5 PR, and stable disease. Median overall survival achieved with venetoclax was 5 months in patients who relapsed and not achieved in patients who were initially treated with venetoclax. Nearly all patients (86.7%) had experienced a grade 2 or more hematologic toxicity. Some 36.7% of these patients had received granulocyte colony stimulating factor (GCSF) support. Infection, mainly pneumonia (26.7%), was the leading nonhematologic toxicity, and fatigue, diarrhea, and skin reactions were the others reported. CONCLUSION: Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML.

BCR-ABL1-Negative Chronic Myeloproliferative Neoplasms and Pulmonary Hypertension: A Prospective Long-Term Follow-up Study of the Impact of Pulmonary Hypertension on Survival.

PURPOSE: To assess the prevalence of PHT in patients with BCR-ABL1-negative CMPN and to evaluate impact of PHT on survival during long-term follow-up. PATIENTS AND METHODS: A total of 122 patients with BCR-ABL1-negative CMPN underwent transthoracic echocardiographic (TTE) evaluation at the beginning of study. Patients undergoing PHT on TTE examination were also evaluated by a pulmonologist. Patients were divided into 3 groups. Group A comprised patients with CMPN-related PHT; group B, patients with no PHT; and group C, patients with PHT due to secondary causes. Patients were evaluated again every 3 to 6 months. RESULTS: PHT was detected in 33 (27%) of 122 patients. Eight (6.5%) had CMPN-related PHT and the remaining 25 (20.5%) had non-CMPN-related PHT. Positivity for JAK2 V617F mutation in the study population was 72.9%. Groups were similar with respect to hematologic parameters and gender. Follow-up times were as follows: median (range) time from diagnosis to TTE and study end were 34 (1-158) months and 107 (16-251) months, respectively, and from TTE to study end was 88 (7-110) months. No significant differences found among the groups in terms of median time from diagnosis to TTE, follow-up, and overall survival. CONCLUSION: BCR-ABL1-negative CMPN patients had a lower prevalence of PHT compared to earlier studies. There was no statistically significant difference in median overall survival between patients with or without PHT. This may be because patients with PHT were asymptomatic and PHT was mild. The impact of PHT on survival was negligible.

Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma.

BACKGROUND: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. PATIENTS AND METHODS: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. RESULTS: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The median duration of response was 4.9 months. The median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. The median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. The depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade ≥ 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. CONCLUSION: The present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

Prognostic Factors in Elderly Patients with Diffuse Large B-Cell Lymphoma and Their Treatment Results

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients.

Long-Term Follow-Up of a Case with Dyskeratosis Congenita Caused by NHP2-V126M/X154R Mutation: Genotype-Phenotype Association.

Dyskeratosis congenita (DC) is a rare inherited syndrome characterized by classical mucocutaneous features and the presence of other clinical features including bone marrow failure, pulmonary fibrosis, liver cirrhosis, and a predisposition to cancer. The symptoms develop at various ages and may manifest over time. Gene mutations associated with DC, such as DC1, TERC, TERT, TINF2, NHP2, NOP10, ACD, CTC1, NAF1, PARN, POT1, RTEL1, STN1, and WRAP53, have been identified in about 70% of patients. Since the number of patients with DC is small and the effect of genetic pathogenic variant may affect the phenotype, we wanted to present the clinical features and course of illness in a patient with NHP2 gene mutation (compound heterozygote for the NHP2 mutations c.376G>A/c.460T>A; amino acid substitutions: p.Val126Met and p.X154Arg) that occurred as a compound heterozygous state.

Is the platelet-to-lymphocyte ratio a new prognostic marker in multiple myeloma?

BACKGROUND: Recent reports showed neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. MATERIALS AND METHODS: We retrospectively examined the PLR, NLR, and MLR in a cohort of 186 newly diagnosed multiple myeloma (MM) patients. This study investigated the prognostic relevance of NLR, PLR, and MLR in MM patients. NLR, PLR, and MLR were calculated from whole blood counts before therapy. The Kaplan-Meier curves and multivariate Cox models were used for the evaluation of survival. RESULTS: Applying cutoff of 1.9 (NLR), 120.00 (PLR), and 0.27 (MLR), decreased PLR showed a negative impact on the outcome. Decreased PLR is an independent predictor for PFS and OS. There were no significant differences in median survival between the high and low NLR (P = 0.80) and MLR (P = 0.87) groups. CONCLUSIONS: In this study, thrombocytopenia and low PLR are associated with poor survival in MM patients does this P value apply to thrombocytopenia or low PLR and may serve as the cost-effective prognostic biomarker.

A Comparison of Fresenius Com.Tec Cell and Spectra Optia Cell Separators for Autologous and Allogeneic Stem Cell Collections: Single Center Experience.

Peripheral blood is the prefered source for hematopoietic stem cells for hematopoietic stem cell transplantation. The efficiency of peripheral blood stem cell (PBSC) collection can vary among devices. In this study we aimed to compare feasibility and effectivity of apheresis procedures of the different systems. Two apheresis systems [Com.Tec (Fresenius Healthcare) and Spectra Optia (Caridian BCT)] were used in our center for the collection of PBSCs for autologous and allogeneic transplantation. We retrospectively analysed 190 apheresis procedures performed in healthy donors and patients between June 2012 and November 2014 in Department of Hematology, Dokuz Eylul University. PBSCS were collected by Fresenius cell separator (64 procedure) or Spectra Optia cell separator (126 procedure). Mobilization treatments were G-CSF (26.8%), cyclophosphamide plus G-CSF (48.4%), prelixafor plus G-CSF (14.7%), ESHAP (10%) and others. Patient and donor characteristics (age, weight, volume processed, disease, mobilization regimes) were similar in Fresenius and Spectra Optia apheresis groups. Altough both collected PBSCs efficiently, the amount of CD34+ cell in product collected by Spectra Optia device was significantly higher (p < 0.05) and product volume was lower than Fresenius Com.Tec significantly (p < 0.05). "CD34+ collection efficiency" with Spectra Optia was significantly higher than Fresenius Com.Tec (CE2: 87%, 70%, p = 0.033) regarding all procedures. High collection efficiency and low product volume may be a significant characteristic of Spectra Optia device (mean 187 mL, product CD34+ cell: 1576 µL).

Can Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio at Day +100 be used as a prognostic marker in Multiple Myeloma patients with autologous transplantation?

BACKGROUND: Recent reports have showed that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are predictors of progression-free survival (PFS) and overall survival (OS) in many types of cancer. This study evaluates the predictive value of NLR, MLR, and PLR for survival in MM patients treated with to ASCT. METHODS: A set of data consisting of 150 patients who underwent autologous stem cell transplantation (ASCT) for MM was collected retrospectively. The prognostic value of NLR, MLR, and PLR was investigated with Kaplan-Meier method. RESULTS: The prognostic value of NLR, MLR, and PLR was analyzed by a receiver operating characteristic (ROC) curve established to determine the cutoff. These cutoff values of NLR, PLR, and MLR were found 1.46, 86, and 0.27, respectively, on the 100th day of post-transplantation period. The overall survival (OS) and the post-transplantation OS of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation were shorter than the other group (P = 0.05, P = 0.018 [NLR], P = 0.05, P = 0.002 [MLR], P = 0.000, P = 0.001 [PLR]). The post-transplantation progression-free survival (PFS) of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation was shorter as well (P = 0.036, P = 0.001, P = 0.001, respectively). CONCLUSION: As increased NLR, MLR, and PLR predicted poor clinical outcome in MM patients with autologous transplantation in this study, they may serve as cost-effective and rapidly available prognostic biomarkers for these patients.

Does Reinfusion of Stem Cell Products on Multiple Days Affect Engraftment?

Objective: High-doses of melphalan treatment with autologous stem cell transplantation in multiple myeloma (MM) remains a major treatment modality in suitable patients. A minimal dose of 2x106/kg CD34+ cells is preferred to achieve engraftment. Some patients need multiple leukapheresis procedures to achieve the necessary number of CD34+ cells, but this can cause a high volume of stem cell product that cannot be given in a single day. Whether or not the number of infusion days affects engraftment has not been studied before. We aimed to evaluate the impact of reinfusion of stem cells on multiple days on engraftment results. Materials and Methods: Demographic features, CD34+ cell doses, neutrophil and platelet engraftment days, hospitalization days, and number of infusion days of 149 autologous transplantations of 143 MM patients were evaluated retrospectively. Results: The data of 143 MM patients who were transplanted were analyzed retrospectively. Median age was 55±8.5 (range: 26-70) years with a male/female ratio of 91/58. Hospitalization days for all patients were 24±6 (range: 14-50) days. Mean CD34+ cell number was (7.5±5.3)x106/kg (range: 1.5-31x106/kg). CD34+ cells were reinfused in 1 day in 80.5% (n=120) of the patients, 2 days in 18.2% of the patients (n=27), and 3 days in 1.3% of the patients (n=2). For 29 patients, reinfusion was applied in more than 1 day because of the high volume of stem cell product. We did not see any dimethyl sulfoxide toxicity, cardiac arrhythmia, or volume overload complications. Hypertensive attacks during infusion were easily controlled by furosemide treatment. In the group with multiple infusions, the infused CD34+ cell numbers had a mean of (4.8±2.8)x106/kg, and in the single infusion group the mean was (8.1±5.5)x106/kg. There were no statistical differences between the two groups regarding platelet and neutrophil engraftment days (p=0.850, r=0.820 and p=0.500, r=0.440). There was no statistical difference between the two groups for hospitalization days (p=0.060, r=0.050). Conclusion: In cases with a high volume of stem cell product to acquire adequate stem cells, reinfusion can be safely applied across multiple days without any delay in engraftment.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Rare Clinical Sign of Hodgkin's Lymphoma: Ocular Involvement.

Bilateral non-granulomatous anterior uveitis with left vitritis and macular edema were detected in a 19-year-old woman presenting with blurred vision in her left eye. Light microscopic study of the pathologic mediastinal lymph node that was detected via contrast computed tomography imaging during etiologic study revealed nodular sclerosing and mixed cellularity Hodgkin's lymphoma (HL). Ocular findings completely resolved with adriablastin, bleomycin, vinblastine, dacarbazine chemotherapy treatment. Herein, it is emphasized that HL should be remembered as one of the differential diagnoses in patients with ocular inflammatory pathologies such as uveitis and vasculitis. The ocular findings of HL are discussed.