Early Tapering of Cyclosporine Is Feasible in Haploidentical Stem Cell Transplantation: A Single Center Experience.

INTRODUCTION: Cyclosporine-A (CsA) and post transplantation cyclophosphamide (PTCy) are common agents used for graft versus host disease (GVHD) prophylaxis in Haploidentical hematopoietic cell transplantation (haplo-HCT). However, the impact of CsA cessation timing in the posttransplant setting on clinical outcomes is uncertain. We aimed to investigate the impact of a novel approach that integrated early CsA cessation with PTCy utilization. PATIENTS AND METHODS: This study was a single arm retrospective study carried out at a tertiary referral hospital hematology and bone marrow transplantation center between 2009 and 2022. The patients who received haplo-HCT with ATG, PTCy and CsA as GVHD prophylaxis were included. CsA was planned for cessation starting at day 45 to day 60. Acute and chronic GVHD were evaluated and graded. CsA blood concentrations and its impact on acute and chronic GVHD was evaluated. RESULTS: Thirty-one patients composed of 19 (61.3%) male and 12 (38.7%) female patients with a median age of 31 years (20-58). Busulfan and TBI based conditioning regimens were the most utilized regimens. The majority of donors were first degree relatives. Stem cell origin was peripheral blood for all patients. GVHD prophylaxis consisted of ATG, CsA and PTCy. Acute GVHD was observed in 9 (29%) cases, whereas chronic GVHD was seen in 3 (9.7%) cases, with 2 of them having overlapping GVHD. Age, gender, number of chemotherapy lines, transplant characteristics, infused CD34 cell count, and engraftment durations were similar among patients with and without GVHD. Patients with GVHD had similar 1st, 2nd, 3rd and 4th week CsA concentrations compared to patients without GVHD (p > 0.05). The presence of GVHD was not associated with worse progression free survival and overall survival (p = 0.6, p = 0.5, respectively). CMV reactivation was more common in the GVHD group. CONCLUSION: In the current study, we did not find an impact of CsA concentration on GVHD and post-transplant outcomes in Haplo-HCT setting. Therefore, together with the use of PTCy, early CsA cessation can be an option; further studies are needed to understand all aspects of this approach.

Is an earlier strategy for harvesting peripheral blood stem cells in healthy allogeneic donors feasible?

INTRODUCTION: Peripheral blood stem cells (PBSC) mobilization with granulocyte colony stimulating factor (G-CSF) for healthy donors is generally performed at 5th day. However, earlier collection is sometimes feasible, raising the question of whether to initiate apheresis early to limit further G-CSF exposure, while considering the risk of mobilization failure. In the current study, we examined the factors predicting successful 4th day collection and developed a model that can be used practically. PATIENTS AND METHODS: The study was carried out by obtaining the data of PBSC mobilizations performed between January 2009 and September 2022 in our transplantation center. RESULTS: A total of 141 healthy donors with a median donor age of 32 (18-64) were included. Adequate mobilization was achieved in 115 (81.6 %) patients. Median peripheral CD34 + cell count was 69.4/µL in the adequate mobilization group and 46/µL in the mobilization failure group (p < 0001). Multivariate analysis revealed that donor/recipient weight ratio and the 4th day peripheral CD34 + cell count≥ 50/µL were independent markers for 4th day collection success. A predictive model of our center including these parameters was available with 0.765 sensitivity and 0.968 specificity [(AUC):0.948 (95 % CI, 0.90-0.99), p < 0.001]. CONCLUSION: The result of the current study shows that peripheral 4th day collection can be performed in selected donors, taking into account peripheral CD34+ cell count and donor/recipient weight ratio. In addition, using these indicators, new predictive models can be created that may assist clinicians in daily practice.

Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from Türkiye

Objective: This study aimed to evaluate patients with relapsed/refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.

Evaluation of oral manifestations and head and neck lymphadenopathy in newly diagnosed acute leukemia patients.

OBJECTIVES: To determine the frequency of head and neck lymphadenopathy (LAP) and intraoral findings (non-dental/dental) in patients with newly diagnosed acute leukemia (AL). SUBJECTS AND METHODS: Twenty-eight (52.8%) females and 25 (47.2%) males in a total of 53 patients with newly diagnosed AL with a mean age of 46 years were included in the study. Personal information, the type of AL (AML [acute myelogenous leukemia]/ALL [acute lymphocytic leukemia]), and hematological findings (anemia, neutropenia, and thrombocytopenia) were obtained from medical records. One of two calibrated oral diagnosis and maxillofacial radiology specialists performed extraoral (head and neck LAPs) and intraoral (non-dental and dental) clinical examinations. The Chi-square (χ2 ) test was used to evaluate categorical variables. RESULTS: LAP was observed in 22.6% and intraoral findings in 30.2% of the patients. LAP was most commonly observed in the neck and none in the parotid glands. The most intraoral findings were gingival/mucosal bleeding and oral petechiae/ecchymosis. While there was no statistical difference between AML and ALL patients in terms of LAP (p > .05), intraoral findings were observed more in patients with AML (p < .05). Only two (3.8%) patients had dental findings. With a slight difference, intraoral findings were more with thrombocytopenia and LAP with neutropenia. CONCLUSION: In AL, especially non-dental intraoral findings are common. The fact that dentists working in the oral cavity are often the first specialists to encounter the oral manifestations of AL imposes an important role in early diagnosis and treatment.

Combination of Venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia: A case series from a single center.

PURPOSE: Venetoclax (VEN) is an oral selective inhibitor of antiapoptotic protein B-cell leukemia/lymphoma-2 (BCL-2). METHODS: We report 7 relapsed/refractory (R/R) acute myeloid leukemia (AML) patients treated with venetoclax and hypomethylating agents (HMA). RESULTS: More than half of the patients could go on with venetoclax for only a few months. CONCLUSION: Using venetoclax combined with HMA in R/R AML should be kept in mind as an alternative salvage option.

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.

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.

Behcet's disease and IgA nephropathy.

Although Behçet's disease (BD) is a kind of systemic disease, renal involvement is rare, especially IgA nephropathy (IgAN). Renal manifestations in BD range from mild urinary abnormalities to glomerulonephritis with persistent renal failure, which includes minimal change disease, proliferative glomerulonephritis, rapidly crescentic glomerulonephritis, renal amyloidosis and IgA nephropathy. Amyloidosis seems to be the most common type of renal lesion in BD, and several cases of nephrotic syndrome secondary to amyloidosis have been documented. Co-occurrence of BD and IgA nephropathy has only been reported in only few cases. We describe two patients with the rare association of BD and IgAN. We suggested that it is important to periodically perform renal function assessment in patients with BD, through urinalysis and measurement of serum creatinine for detecting any abnormality and providing an early adequate treatment.

Mucocutaneous manifestations in inflammatory bowel disease.

BACKGROUND: The aim of this study was to evaluate the prevalence and features of the major cutaneous manifestations (erythema nodosum [EN] and pyoderma gangrenosum [PG]) and to determine the associations between cutaneous manifestations and other extraintestinal manifestations in patients with inflammatory bowel disease (IBD). METHODS: The mucocutaneous manifestations of patients with IBD were studied between December 2002 and June 2007. All patients underwent a detailed whole body examination by a gastroenterologist and dermatologist. RESULTS: In all, 352 patients were included in this study; 34 patients (9.3%) presented with at least 1 major cutaneous manifestation. The prevalence of EN (26 patients) and PG (8 patients) in IBD was 7.4% and 2.3%, respectively. EN was more common in Crohn's disease (16/118) than ulcerative colitis (10/234) (P = 0.002). EN was found to be related to disease activity of the bowel (P = 0.026). The prevalence of arthritis was significantly higher in the IBD patients with EN (11/26) than in IBD patients without EN (53/326) (P = 0.006). Arthritis was more common in IBD patients with PG (7/8) than in IBD patients without PG (57/344) (P = 0.00). IBD patients with PG were significantly more likely to have uveitis (1/8) compared with IBD patients without PG (5/344) (P = 0.017). CONCLUSIONS: We found the prevalence of 2 important cutaneous manifestations to be 9.3% in IBD in Turkish patients. EN was found to be more common in Crohn's disease and is associated with an active episode of bowel disease and peripheral arthritis. In addition, PG was connected with uveitis and peripheral arthritis.