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 neutropenic fever an obstacle to effective stem cell harvesting?

INTRODUCTION: Autologous stem cell transplantation (ASCT) is a well-established consolidation treatment for many hematologic cancers which delivers prolonged survival. A subset of patients' adequate stem cell harvest is not achievable with a solitary use of granulocyte colony-stimulating agents (G-CSF). Generally, chemomobilization is employed for patients failing G-CSF and its most feared complication febrile neutropenia (FN). MATERIALS AND METHODS: Here, we aimed to investigate the impact of the FN in chemomobilization on apheresis outcomes and engraftment. One hundred and eighty-three patients with the diagnosis of lymphoma or myeloma who underwent chemomobilization between 2015 and 2020 were included in the study. RESULTS: Forty-three patients experienced FN. All patients received G-CSF. All myeloma patients were mobilized with 4 g/m2 cyclophosphamide, but it was heterogeneous for lymphoma patients. The precollection blood counts, harvested CD34+ hematopoietic stem cells (HSCs)/kg, apheresis count, and engraftment durations were recorded. Preapheresis leukocyte and platelet were lower in the FN group (P = 0,004 and P = 0,001). Peripheral CD34 HSCs and total harvested CD34 HSCs were similar among groups (P = 0.25 and P = 0.9). More apheresis was needed in the FN group, but it was not significant (P = 0.07). Undergoing ASCT was similar (P = 0.7); however, platelet and neutrophil engraftment durations were slower in the FN group (P = 0.05 and P = 0.001). CONCLUSION: Harvesting sufficient CD34+ HSCs from patients with FN is still feasible; however, FN treatment should begin promptly, and further apheresis sessions may be required.

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.

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.

An effective treatment in Erdheim Chester disease: vemurafenib: a case report.

BACKGROUND: Erdheim Chester disease (ECD) is a rare disease with multisystemic involvement in the group of non-langerhans cell histiocytosis. Although nearly 100 years have passed since its definition, the number of cases reported all over the world is below 1000. In addition to the rarity of the disease, low awareness seems to play a role in this. CASE PRESENTATION: 47-year-old white caucasian women patient who presented to our clinic with symptoms of weakness-fatigue as well as increasing pain in the knees and ptosis in the left eye. Result of the patient's bone biopsy, ECD was considered pathologically and BRAF V600E mutation was shown molecularly. After presenting the clinical, laboratory and other examination results of the case, the dramatic response seen with targeted therapy will be discussed. CONCLUSIONS: BRAF V600E mutation is frequently seen in ECD. Vemurafenib plays an active role in targeted therapy.

COVID-19 in cancer patients: patient characteristics and outcomes in the post-COVID-19 vaccination period.

Background/aim: It wasaimed herein to investigate coronavirus disease (COVID-19) in cancer patients and compare hematological and solid organ cancer patients in terms of the course and outcome of this disease. Materials and methods: Data from cancer patients with laboratory-confirmed COVID-19 infection were analyzed retrospectively. Risk factors for poor prognosis and the effect of vaccination on the clinical outcomes of the patients were evaluated. Results: A total of 403 cancer patients who were diagnosed with COVID-19 between March 1st, 2021, and November 30th, 2022, were included, of whom 329 (81.6%) had solid and 74 (18.4%) had hematological cancers. Hospitalization and intensive care unit (ICU) admission rates were significantly higher in the hematological cancer patients compared to the solid organ cancer patients (73.0% vs. 35.9%, p< 0.001 and 25.7% vs. 14.0%, p= 0.013, respectively). The COVID-19-related case fatality rate (CFR) was defined as 15.4%, and it was higher in the hematologicalcancer patientsthan inthe solid organ cancer patients (23.0% vs. 13.7%, p= 0.045) and was higher in patients with metastatic/advanced disease compared to the other cancer stages (p< 0.001). In the solid organ cancergroup, hospitalization, ICU admission, and the COVID-19 CFR were higher in patients with respiratory and genitourinary cancers (p< 0.001). A total of 288 (71.8%) patients had receivedCOVID-19 vaccination; 164 (56.94%) had≤2 doses and 124 (43.06%) had≥3 doses. The hospitalization rate was higher in patients with ≤2 doses of vaccine compared to those with ≥3 doses (48.2% vs. 29.8%,p= 0.002). Patients with COVID-19-related death had higher levels of leucocyte, neutrophil, D-dimer, troponin, C-reactive protein (CRP), procalcitonin, and ferritin and lower levels of lymphocyte than the survivors. In the logistic regression analysis,the risk of COVID-19-related mortality was higher in the hematological cancer patients(OR:1.726), those who were male (OR:1.757), and with the Pre-Delta/Delta variants (OR:1.817). Conclusion: This study revealed that there is an increased risk of COVID-19-related serious events (hospitalization, ICU admission, or death) in patients with hematological cancerscompared with those who have solid organ cancers. It wasalso shown that receiving ≥3 doses of COVID-19 vaccine is more protective against severe illness and the need for hospitalization than ≤2 doses.

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.