Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes.

INTRODUCTION: Allogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors' age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality. METHOD: Sixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009-2019 were enrolled for the study. All donors received 4-5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50-54 group A, 55-59 group B, aged 60 and older group C. RESULTS: Pre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5). CONCLUSION: Adequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.

Recovery of Symmetrical Peripheral Gangrene of Limbs in a Patient After Performing Hemoadsorption in Septic Shock.

We report a 42-year-old patient who had Hodgkin lymphoma and developed bilateral symmetrical peripheral gangrene (SPG) in the feet and hands, which occurred during septic shock after autologous hematopoietic stem-cell transplantation. SPG is a rare but severe complication of disseminated intravascular coagulation (DIC) and is frequently associated with sepsis. The pathophysiology of SPG includes DIC-mediated intravascular thrombosis and thrombotic occlusion of microcirculation, resulting in low blood flow. Sepsis-induced hypotension has been suspected as one of the other causes of SPG, and it is thought to be aggravated by vasopressor treatments given for hypotension. Our patient first experienced coldness, paleness, and cyanosis in his body's acral parts, and then SPG later developed in both his feet and hands. Septic shock management was performed with cytokine hemoadsorption, broad-spectrum antibiotics, and massive fluid replacement rapidly. The patient fully recovered without the need for amputation. Hemoadsorption is an extracorporeal cytokine-adsorption method for removing excess cytokines. Prompt management of septic shock and early monitoring of peripheral ischemia are essential to avoid SPG.

Gemcitabine, dexamethasone and cisplatin (GDP) is an effective and well-tolerated mobilization regimen for relapsed and refractory lymphoma: a single center experience

Background/aim: Gemcitabine, dexamethasone and cisplatin (GDP) is a well-established salvage regimen for relapsed and refractory lymphomas. In this study, we aimed to share our experience with the patients who received GDP/R-GDP (rituximab-gemcitabine, dexamethasone and cisplatin) for stem cell mobilization. Materials and methods: Data of 69 relapsed and refractory Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) patients who received GDP/R-GDP as salvage chemotherapy in our center between July 2014 and January 2020 were retrospectively evaluated. After the evaluation of response, 52 patients had a chemosensitive disease and underwent mobilization with GDP/R-GDP plus G­CSF (granulocyte colony-stimulating factor). Collected CD34+ stem cells and related parameters were compared in terms of diagnosis of HL and NHL, early and late stage, patients who did not receive RT and those who received RT, and patients aged under 60 and over 60. Results: On the 15th day on average (range 11­20), a median number of 8.7 × 106 /kg (4.1­41.5) CD34+ stem cells were collected in 51 (98%) of our 52 chemosensitive patients and 1 (2%) patients failed to mobilize. We observed acceptable hematological and nonhematological toxicity. The targeted amount of 2 × 106 /kg CD34+ stem cells was attained by 98% (n: 51) patients, and all of them underwent autologous stem cell transplantation. Moreover, low toxicity profiles provide outpatient utilization option clinics with close follow-up and adequate supportive care. Conclusion: We suggest that GDP/R-GDP plus G-CSF can be used as an effective chemotherapy regimen for mobilizing CD34+ stem cells from peripheral blood in relapsed and refractory lymphoma patients due to low toxicity, effective tumor reduction, and successful stem cell mobilization. It can also be assumed that the GDP mobilization regimen may be more effective, especially in patients with early-stage disease and in HL patients.

The effect of gemcitabine, dexamethasone, and cisplatin chemotherapy in relapsed/refractory NHL and HL patients: A single center experience.

The optimal choice of salvage therapy for patients with relapsed/refractory non-Hodgkin lymphoma or Hodgkin lymphoma remains controversial. In this study, we aimed to share our experience in relapsed/refractory lymphoma patients who received GDP/R-GDP as salvage chemotherapy in our center. Data of 47 relapsed/refractory Hodgkin lymphoma and non-Hodgkin lymphoma patients who received GDP or R-GDP as salvage chemotherapy in our center between July 2014 and October 2017 were retrospectively evaluated. Non-Hodgkin lymphoma and Hodgkin lymphoma patients were divided into two groups as primary refractory and relapsed. The one-year overall survival was 100% (for relapsed) and 36.9% (for refractory) in the non-Hodgkin lymphoma groups, and 82.5% (for relapsed) and 80% (for refractory) in the Hodgkin lymphoma group. The one-year progression-free survival (PFS) was 72.7% (for relapsed) and 38.5% (for refractory) in patients with NHL, and 41% (for relapsed) and 18.2% (for refractory) in patients with HL. GDP/R-GDP seems to be a well-tolerated out-patient salvage regimen for relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma. Although proven efficacy, negative toxicity profile, and ease of administration, the application of gemcitabine-based therapy for patients with primary refractory non-Hodgkin lymphoma and Hodgkin lymphoma provided limited success.

Does microbial contamination influence the success of the hematopoietic cell transplantation outcomes?

INTRODUCTION: Microbial contamination can be a marker for faulty process and is assumed to play an important role in the collection of hematopoietic progenitor cell (HPC) and infusion procedure. We aimed to determine the microbial contamination rates and evaluate the success of hematopoietic cell transplantation (HCT) in patients who received contaminated products. PATIENTS-METHODS: We analyzed microbial contamination records of HPC grafts between 2012 and 2015, retrospectively. Contamination rates of autologous donors were evaluated for at three steps: at the end of mobilization, following processing with dimethyl sulfoxide, and just before stem cell infusion. Grafts of allogeneic donors were assessed only before HCT. RESULT: A total of 445 mobilization procedures were carried out on 333 (167 autologous and 166 allogeneic) donors. The microbiological contamination of peripheral blood (323/333 donations) and bone marrow (10/333 donations) products were analyzed. Bacterial contamination was detected in 18 of 1552 (1.15 %) culture bottles of 333 donors. During the study period 248 patients underwent HCT and among these patients microbial contamination rate on sample basis was 1.3 % (16/1212). Microbial contamination detected in nine patients (7 autologous; 2 allogeneic). In 8 of 9 patients, a febrile neutropenic attack was observed. The median day for the neutropenic fever was 4 days (0-9). None of the patients died within the post-transplant 30 days who received contaminated products. CONCLUSION: The use of contaminated products with antibiotic prophylaxis may be safe in terms of the first day of fever, duration of fever, neutrophil, platelet engraftment and duration of hospitalization.

Latent tuberculosis in adult hematopoietic stem cell transplantation recipients: Clinical experience from a previously endemic population.

Hematopoietic stem cell transplantation (HSCT) recipients may be at an elevated risk of developing active tuberculosis infection due to suppression in the cellular immune system. Herein, we aimed to evaluate the prevalence of latent tuberculosis and active tuberculosis in patients with allogeneic and autologous HSCT. In this cohort, data were obtained retrospectively from patients' records. The patients who were followed up in the bone marrow transplantation unit of the University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital between January 2016 and December 2019 were screened for the study. And the HSCT recipients who had tuberculin skin test and/or QuantiFERON-TB gold (QFT-GIT) test results were included in the study. A total of 361 patients were included in the study, 227 patients had autologous HSCT, and 134 patients had allogeneic HSCT. QFT-GIT was performed in 10 patients with allogeneic HSCT, and it was found positive in only 1 patient. Tuberculin skin test ≥5 mm was accepted as positive and was accepted to have latent tuberculosis, and it was positive in 18.2% (41) of the patients with autologous HSCT and was positive in 21.6% (29) of the patients with allogeneic HSCT. There was no significant difference between the 2 groups (P = .429). Isoniazid (INH) prophylaxis was started in 16.7% of patients with autologous HSCT and 22.4% of patients with allogeneic HSCT. During follow-up, active tuberculosis did not develop in any patients in both groups. There was no statistically significant difference found between allogeneic and autologous HSCT recipients regarding the prevalence of latent tuberculosis. Active tuberculosis infection did not develop in any of the patients who started INH prophylaxis. INH prophylaxis seems to be very efficient in preventing the reactivation of latent tuberculosis in patients going through allogeneic HSCT and/or autologous HSCT.

Brentuximab vedotin and bendamustine: an effective salvage therapy for relapsed or refractory Hodgkin lymphoma patients.

The prognosis is poor for relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL) patients. The brentuximab vedotin (Bv) and bendamustine (B) combination has been used as a preferable salvage regimen in R/R cHL patient trials. We retrospectively evaluated response rates, toxicities, and the survival in R/R cHL patients treated with the BvB combination. In a multi-centre real-life study, 61 R/R HL patients received intravenous doses of 1.8 mg/kg Bv on the first day plus 90 mg/m2 B on the first and second days of a 21-day cycle as a second-line or beyond-salvage regimen. Patients' median age at BvB initiation was 33 (range: 18-76 years). BvB was given as median third-line treatment for a median of four cycles (range: 2-11). The overall and complete response rates were 82% and 68.9%, respectively. After BvB initiation, the median follow-up was 14 months, and one- and two-year overall survival rates were 85% and 72%, respectively. Grade 3/4 toxicities included neutropenia (24.6%), lymphopenia (40%), thrombocytopenia (13%), anaemia (13%), infusion reactions (8.2%), neuropathy (6.5%), and others. The BvB combination could be given as salvage regimen aiming a bridge to autologous stem cell transplant (ASCT), in patients relapse after ASCT or to transplant-ineligible patients with manageable toxicity profiles.

The effect of bulky mass on prognosis in diffuse large-B-cell lymphoma: still poor?

The introduction of rituximab to the CHOP protocol has demonstrated an improvement in PFS and OS in DLBCL patients with both early and advanced stages. Most studies in the pre-rituximab period indicated that bulky disease has an unfavorable impact on clinical outcomes of DLBCL. The effect of bulky mass on the outcome of DLBCL patients undergoing R-CHOP therapy remained uncertain. One-hundred-twelve newly diagnosed DLBCL patients aged 18 and older were enrolled in the study. Patients were divided into groups-based presence of bulky disease. 56 patients with bulky disease and their age, gender, ECOG score, Ann Arbor stage, immunohistochemical origin, treatment, radiotherapy and comorbidity 1:1 matched 56 control patients with non-bulky disease included. Overall response rate at end of treatment was similar among groups (p = 0.1). Patients with bulky disease and non-bulky disease were comparable regarding overall survival (p = 0,9). All cohort investigated for predictors for survival, after multivariate analysis, ECOG score, Ann arbor stage, IPI score and LDH level were found significant. Here, we found no impact of bulky disease on remission and survival. We believe, with increasing available data, poor prognostic value of bulky disease will be weakening in the rituximab era.

The Outcome of Diffuse Large B Cell Lymphoma Patients in Adolescent and Young Adult Age Group.

Purpose: In the literature, substantial differences have been reported regarding incidence and outcomes for the pediatric and adult groups with non-Hodgkin's lymphoma (NHL). Diffuse large B cell lymphoma (DLBCL) is the most common NHL subtype, and its outcome in adolescents and young adults (AYA) has not been widely investigated. This study aims at reporting our experience on the outcome of DLBCL in the AYA group. Methods: One hundred twenty DLBCL patients, 40 AYA patients, and 1:2 matched 80 control non-AYA patients were diagnosed and followed up at our center included. Results: In both groups, the median progression-free survival (PFS) and overall survival (OS) were not reached, without any difference between groups (p = 0.7, p = 0.7, respectively). The median follow-up time was 28 (range 1-133) months in all patients. In both groups, international prognostic index scores and early relapse were associated with worse PFS and OS, but in the non-AYA group, the immunohistologic type was, in fact, related to worse outcomes. Conclusion: DLBCL in AYA is a predominantly overlooked subject, due to the rarity of the disease. The outcome of DLBCL in this age group is not encouraging, which not only needs to be further investigated, but novel approaches must also be developed.

Does Total Body Irradiation Have a Favorable Impact on Thrombocyte Engraftment as per Neutrophil Engraftment in Allogeneic Stem Cell Transplantation?

INTRODUCTION: In this study, we aim to analyze the effect of total body irradiation (TBI) on neutrophil and thrombocyte engraftment durations in acute leukemia (AL) patients who achieved allogeneic hematopoietic stem cell transplantation (Allo-SCT) at our center. METHODS: The data of 193 acute leukemia patients who were performed Allo-SCT from matched-related donors were analyzed retrospectively. RESULTS: Thrombocyte engraftment duration was statistically shorter (12 days) in acute lymphoblastic leukemia (ALL) patients who received TBI-based conditioning when compared to ALL patients who received non-TBI-based conditioning (14 days; p=0.037). On the other hand, no statistically significant difference was observed between acute leukemia patients who received TBI or non-TBI-based conditioning regarding neutrophil engraftment duration. CONCLUSION: We found that TBI had a favorable impact on thrombocyte engraftment (TE) rather than neutrophil engraftment (NE) in Allo-SCT in patients with acute leukemia. TBI might have an impact on the engraftment of thrombocytes as per than neutrophils may be attributed to immune mechanisms and microenvironment in the patient's bone marrow (BM).

Molecular evaluation of mutations in acute myeloid leukemia patients from Turkey: A single-center study.

ABSTRACT: Certain genetic mutations could have a role in the etiology of acute myeloid leukemia (AML). Hereby, in this study, we primarily aimed to investigate the distribution of genetic mutations in AML patients. We also attempted to analyze the incidence of genetic mutations in AML patients from Turkey.This retrospective study included a total of 126 patients diagnosed with AML, who had molecular mutation test results or records in their patient files. The patients who were not citizens of the Republic of Turkey were not included in the study.It was observed that analyses for at least 1 c-kit exon mutation had been carried out on 76 patients, which detected no c-kit mutation among the types of genetic mutations investigated in all of those 76 patients. We found the frequency of FMS-like tyrosine kinase 3-internal tandem duplication mutation as 25%. The prevalence of translocation(15;17) was approximately 11% and the prevalence of translocation(8;21) was % 6.25. In addition, we also showed that the frequency of inversion16 was nearly 3.7%.Lastly, the possibility of c-kit mutation in AML patients from Turkey might actually be low.

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.