Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey.

Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8 mg/kg, rituximab 375 mg/m2 on day 1, and bendamustine 90 mg/m2 on days 1-2 of each cycle. Median age at Pola-BR initiation was 55 (19-84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5 months, the median OS was 5 months. Grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile.

Could blood groups have prognostic significance on survival in patients with diffuse large B cell lymphoma?

The prognostic importance of the ABO blood group in non-Hodgkin lymphoma is largely unknown. We aim to investigate the prognostic significance of blood groups on the survival in diffuse large B-cell lymphoma (DLBCL) patients. 412 people (206 DLBCL patients and 206 healthy donors) were included. The blood group types of patients treated at our center from 2009 to 2019 were analyzed retrospectively and compared to the results from healthy thrombocyte donors. The distribution of the ABO blood groups was as follows: blood type A (45.2%), B (9.7%), O (38.8%), and AB (6.3%). We found no statistically significant difference between patients and the control group in terms of ABO and Rhesus blood group distribution (p = 0.27 and p = 0.45, respectively). The median follow-up time was 18 months (0-116). In the Cox regression analysis ABO blood groups, and Rh group were not significant predictors of survival in patients with DLBCL, whereas ECOG score, IPI score, Ann-Arbor stage, and LDH level were found significant. Receiving R-CHOP as the first-line treatment was associated with better survival in the multivariate analysis. No statistically significant difference was found between the control and DLBCL patient groups regarding the distribution of ABO and Rh blood groups.

Single-Dose Rasburicase Might Be Adequate To Overcome Tumor Lysis Syndrome In Hematological Malignancies.

INTRODUCTION: Tumor lysis syndrome (TLS) is a commonly observed oncological emergency that requires prompt diagnosis and treatment. Rasburicase is a recombinant urate oxidase endorsed in TLS for the treatment of hyperuricemia. The effect of single-dose 7.5 mg rasburicase at longer follow-ups was not widely investigated. PATIENTS AND METHODS: Eighty-two patients included in the study with clinical TLS and laboratory TLS. The primary endpoint was the normalization of uric acid (<6mg/dL) within 24 hours of rasburicase administration, which was described as treatment success. The secondary endpoint was defined as having sustained response at the first week. The third endpoint was defined as the reaching the baseline renal function before TLS. RESULTS: We found that the use of a 7.5 mg dose of rasburicase controlled uric acid in 74 of 82 (90,2%) patients at the 24th hour. In the first week, uric acid remained at normal levels in 69 of 82 (84,1%) patients. At 24 hours, the TLS risk group was the only predictor for failing uric acid normalization; at the end of the first week, no predictive factor was identified for failing uric acid normalization. CONCLUSION: Rasburicase at 7.5 mg dose is an important agent for controlling laboratory and clinical TLS at 24 hours and extending its effect to the first week.

Factors affecting survival in elderly patients with diffuse large B-Cell lymphoma.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) has an increasing incidence in elderly patients with poorer prognosis than in younger patients. Clinicians should clearly identify the characteristics and prognostic factors of elderly patients. We analyzed the outcome of elderly DLBCL patients, especially factors affecting survival in real-life clinical practice. MATERIALS AND METHODS: The data of 330 DLBCL patients at our center were retrospectively evaluated by dividing three groups; younger than 65 years, between 65-79 years, and 80 years and older. We examined the factors affecting survival in DLBCL patients ≥ 65 years old. RESULTS: The median age of the patients was 61 years (range 16-87). 192 (58.2 %) of our patients were younger than 65 years old, 112 (33.9 %) were between 65-79 years, and 26 (7.9 %) patients were 80 years old or older. The median follow-up was 15 (1-120) months. Median PFS was 38 months in the 65-79 years group, ten months in the ≥ 80 years group; meanwhile, median OS was 43 months in the 65-79 years group, 25 months in the ≥80 years group. The number of patients who relapsed within 12 months of the first-line treatment was 69 (35.9 %) in the <65 years group, it was 60 (53.6 %) in 65-79 years group, and 22 (84.6 %) in ≥80 years group (p < 0.001). The median OS was 9 (7.1-10.9) months in DLBCL patients older than 65 years old who relapsed within 12 months. Early relapse, failure to achieve CR after first-line chemotherapy, and high IPI score were associated with poor survival in patients ≥ 65 years old (p:0.001). CONCLUSION: Advancing age was a poor prognostic factor for survival of DLBCL. Relapsing within the first year, or failure to achieve complete remission were associated with poorer survival of the elderly DLBCL patients. R-CHOP is the standard treatment in DLBCL, and the best responses are obtained regardless of age. Due to difficulty in receiving standard treatments, novel treatment modalities are needed for better outcomes in elderly patients with DLBCL.

Does myeloma genetic have an effect on stem cell mobilization?

BACKGROUND: Autologous stem cell transplantation (ASCT) after induction treatment is the standard of care. Our understanding of myeloma genetics has been very limited and its effect to stem cell mobilization is not widely investigated. We aimed to investigate the effect of genetic abnormalities on stem cell mobilization in myeloma. METHODS: The data of 150 MM patients who underwent stem cell mobilization at our center between 2009-2020 were included and analyzed retrospectively. Pre-treatment bone marrow cytogenetics and fluorescence in situ hybridization tests were performed for each patient. RESULTS: Groups were divided into two as patients with normal cytogenetic and abnormal cytogenetic. No difference observed between groups regarding age, gender and ECOG (p = 0.4; p = 0.2; p = 0.3). Groups were similar concerning myeloma characteristics, received treatment and treatment response. Median CD34+ cells/kg harvested was 444(2-11.29) in normal cytogenetic group whereas it was 4,8(2.4-8.6) in abnormal cytogenetic group(p = 0.2). Optimal CD34+ cells level achievement was 73 (67 %) in normal cytogenetic group while it was 25(71.4 %) in abnormal cytogenetic group(p = 0.6). Neutrophil and platelet engraftment durations were similar among cytogenetic groups (p = 0.7; p = 0.9). R-ISS based groups were also did not differ regarding harvested CD34+ cells and achievement optimal CD34 level (p = 0.79, p = 0.74). Engraftment durations for neutrophil and platelet were comparable between R-ISS based groups (p = 0.59, p = 0.65) CONCLUSIONS: Here we were not able to find any impact of genetic abnormalities on stem cell mobilization in myeloma patients. Expanded studies can aid to identify the effect of particular genetic anomalies on the stem cell mobilization.

Analysis of pre-chemotherapy WBC, PLT, monocyte, hemoglobin, and MPV levels in acute myeloid leukemia patients with WT1, FLT3, or NPM gene mutations.

Effects of mutations on AML (acute myeloid leukemia) patients have been an area of clinical interest. The aim of this study was to analyze pre-chemotherapy WBC (white blood cell), platelet, monocyte, hemoglobin, and mean platelet volume (MPV) levels in acute myeloid leukemia patients with Wilms tumor 1 (WT1), FMS-like tyrosine kinase 3 (FLT3), or nucleophosmin (NPM) gene mutations, attempting to detect and compare possible differences in these values.The study included 71 patients with acute myeloid leukemia known to have WT1, FLT3, or NPM gene mutations. The patients were divided into 3 groups: FLT3-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 1), NPM-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 2), WT1-mutated AML patients with no other accompanying known mutations at the time of diagnosis (Group 3). We carried out intergroup comparisons of WBC, platelet (PLT), monocyte, hemoglobin, and MPV levels before chemotherapy.There was a statistically significant difference between the groups in terms of WBC parameters (P = .001). There were no statistically significant differences between the groups with respect to hemoglobin, platelet, and monocyte levels.Higher white blood cell counts could be observed in patients with FLT3-mutated AML.

The effect of serum vitamin B12, folate, ferritin levels and transferrin saturation on stem cell mobilization in allogeneic donors.

INTRODUCTION: Peripheric blood derived stem cells are used in 75 % of allogeneic stem cell transplantations. Iron, vitamin B12 and folate involve in hematopoiesis. Therefore serum levels of iron, vitamin B12 and folat may effect stem cell mobilization. We aimed to analyze the effects of iron status, vitamin B12 and folate levels on peripheric blood stem cell mobilization in healthy donors. METHOD: The mobilization results of 218 allogeneic donors were analyzed retrospectively. RESULTS: In 64 donors, serum ferritin level was <15 µg / L and transferrin saturation was <20 %. When we compared the donors with iron deficiency to the donors without iron deficiency, the number of collected CD34 + cell was significantly higher in donors without iron deficiency. We did not find any impact of serum vitamin B12 and folate level on CD34+ cells collected. CONCLUSION: Our study shows that serum ferritin and transferrin saturation have a greater effect on the amount of CD34+ cells collected from donors than serum vitamin B12 and folate levels. Consequently, when compliance tests of allogeneic donors are performed, the evaluation of vitamin B12 and folate levels is not necessary; whereas iron deficiency must be assessed and -if possible- corrected before apheresis is performed.

Inferior prognosis in poor mobilizing myeloma patients.

INTRODUCTION: Induction treatment followed by autologous stem cell transplantation (ASCT) has been accepted as the standard treatment for multiple myeloma (MM) patients. Granulocyte colony stimulating agent (G-CSF), chemotherapy or agents likes plerixafor are being used for the mobilization of stem cells from bone marrow. In this study, we evaluated the impact of the mobilization methods on the outcome of MM patients after ASCT. METHOD: The data of 205 MM patients who underwent ASCT at our center between December 2009 and January 2019 were retrospectively analyzed. Patients were divided into 2 groups as good mobilizers (patients who were mobilized with G-CSF alone) and poor mobilizers (patients who were failed to mobilize with G-CSF alone and mobilized with G-CSF + cylophosphomide or G-CSF + plerixafor). RESULTS: The median progression free survival (PFS) was 18.27 ± 3.22 months in good mobilizers and 14.22 ± 3.7 months in poor mobilizers. In G-CSF + cyclophosphamide method median PFS was 15.4 ± 4.9 months wheras it was only 4 months in G-CSF + plerixafor method. We did not find a statistically significant difference between good and poor mobilizers regarding median PFS (p: 0.342). The median overall survival (OS) was found 34.48 ± 4.2 months in good mobilizers and 15.13 ± 5.78 months in poor mobilizers. In G-CSF + cyclophosphamide method median OS was 17 ± 14.01 months wheras it was 10.66 ± 7.68 months in G-CSF + plerixafor method. We found a statistically significant difference between good and poor mobilizers regarding median OS (p: 0.007*). CONCLUSION: Our study shows that difficulty in stem cell mobilization is correlated with worse outcome.

Evaluation of neutropenia-related outcomes in Hodgkin's lymphoma patients with moderate or severe neutropenia who received ABVD chemotherapy without using granulocyte-colony stimulating factor.

OBJECTIVE: To evaluate the possible neutropenia-related effects of administering adriamycin [doxorubicin], bleomycin, vinblastin, dacarbazine (ABVD) chemotherapy in Hodgkin's lymphoma patients with moderate or severe neutropenia without granulocyte-colony stimulating factor supplementation. METHODS: This study evaluated neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use during the periods between chemotherapy rounds. Forty-three rounds of ABVD chemotherapy were evaluated in the study. The outcomes that could be related to neutropenia were analyzed. In addition, rounds of ABVD chemotherapy given in the presence of severe neutropenia were compared with ABVD chemotherapy rounds given in the presence of moderate neutropenia in terms of neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use. The study only included patients with classical Hodgkin's disease (lymphoma). Patients with a final neutrophil count of <1 × 103 cells/µL (<1000 cells/µL) prior to chemotherapy round and those receiving ABVD chemotherapy for Hodgkin's lymphoma were included in the study. RESULTS: We observed that none of the patients with moderate neutropenia before the start of chemotherapy round needed granulocyte-colony stimulating factor, and four patients with severe neutropenia prior to the start of chemotherapy round required granulocyte-colony stimulating factor. However, there was no statistically significant relationship between the severity of neutropenia (in terms of moderate and severe) before chemotherapy and granulocyte-colony stimulating factor requirement after chemotherapy (p> 0.05). Furthermore, none of the patients included in the study had bleomycin-related lung toxicity during the treatment periods included in the study. CONCLUSION: Administering ABVD chemotherapy to patients with moderate neutropenia seems to be safe.

Pralatrexate induced durable response in a relapsed/refractory peripheral T-cell lymphoma patient with a history of autologous stem cell transplantation: Case report of a patient followed-up over 3 years under pralatrexate treatment.

RATIONALE: Relapsed or refractory peripheral T-cell lymphomas are aggressive diseases. Pralatrexate is an antimetabolite. Hereby, we are reporting a pralatrexate induced durable response in a relapsed/refractory peripheral T-Cell lymphoma patient with a history of autologous stem cell transplantation. PATIENT CONCERNS: A male patient born in February 1947 was diagnosed with lymphoma based on his cervical lymph node excisional biopsy. DIAGNOSES: He was diagnosed with PTCL-NOS on February 19, 2013. INTERVENTIONS: The patient received 6 cycles of CHOP (Cyclophosphamide, doxorubicine, vincristine, methylprednisolone) chemotherapy, which achieved a complete remission. The patient underwent autologous stem cell transplantation in December 2013. After relapse was detected in the third month of the transplantation, the patient was treated with 2 cycles of ViGePP (vinorelbine, gemcitabine, procarbazine, prednisone/ methylprednisolone) chemotherapy. The patient was considered refractory to treatment after the ViGePP chemotherapy, and he was given brentuximab vedotin. Once a full response to treatment was achieved after 2 cycles, the patient received 6 cycles of brentuximab vedotin treatment. After 6 cycles, a skin biopsy was performed and the patient was diagnosed with relapsed/refractory PTCL-NOS. Pralatrexate therapy was then started on February 1, 2016 at a dose of 30 mg/m once weekly for 6 weeks in 7-week cycles. OUTCOMES: The patient responded to pralatrexate treatment. And he has been under pralatrexate treatment over 3 years. LESSONS: Pralatrexate should also be kept in mind as a treatment alternative in relapsed or refractory peripheral T-cell lymphoma patients.

Monoclonal B-cell lymphocytosis in blood donors in Turkey.

OBJECTIVES: Monoclonal B-cell lymphocytosis (MBL) is a precursor state of chronic lymphocytic leukemia (CLL) with peripheral lymphocytosis below 5 × 109/l. The diagnostic criteria exclude the presence of lymphadenopathy, organomegaly, infections, autoimmune diseases or any sign of a lymphoproliferative disorder. This prospective study was designed in order to evaluate the frequency of MBL in blood donors in Turkey. METHODS: The diagnosis of MBL was identified by flow cytometry method based on the International Familial CLL Consortium Report. A total of 999 volunteers [median age 34 (18-78) years; male/female: 705/294] were included in the study. RESULTS: Monoclonal B-cell lymphocytosis was demonstrated in 18 cases (1.8%). A total of 16 cases (1.6%) was evaluated as CLL-like MBL, while 2 (0.2%) had a non-CLL-like phenotype. The subjects were divided into three groups according to age, as <40 years, 40-60 years and >60 years. The prevalence of MBL was 1.1% below 40 years, 0.6% between 40 and 60 years and 0.1% in cases over 60 years, without statistical significance (p > 0.05). DISCUSSION: The sensitivity of the flow cytometry method is essential and may be responsible for the variations in the prevalence of MBL in different populations which can also be attributed to study design, higher detection rates in the elderly and families with genetic predisposition to CLL. CONCLUSION: Large population-based studies and standardized laboratory methods are needed to determine the potential risk factors of progression to CLL, including molecular markers and genetic profile.