Comparison of Clinical and Hematological Parameters of Janus Kinase 2, Calreticulin or Myeloproliferative Leukemia Virus Oncogene Mutant Essential Thrombocythemia and Triple-Negative Essential Thrombocythemia.

Introduction Essential thrombocythemia (ET) is one of the chronic myeloproliferative neoplasms. While Janus kinase 2 (JAK2) V617F mutation is defined in more than half of the patients with ET, calreticulin (CALR) or myeloproliferative leukemia virus oncogene (MPL) mutations are encountered more rarely. The discovery of the JAK2 V617F mutation in 2005, followed by the recognition of MPL and CALR mutations, brought up the idea of subdividing ET according to the mutation status. Our aim in this study is to investigate whether genetic mutations detected in patients diagnosed with ET cause a different clinical phenotype compared to triple-negative ET. Methods This retrospective study was conducted by evaluating the patients who were followed up with the diagnosis of ET in the hematology clinic of two tertiary centers in Turkey between 2009 and 2021. Patients with negative JAK2, CALR, and MPL mutations and meeting the diagnostic criteria for ET were defined as triple-negative ET. The patients were divided into two groups as triple-negative ET and mutation-positive ET according to the presence of a mutation. It was investigated whether there was a difference between these two groups in terms of demographic, laboratory, and clinical characteristics. Results A total of 109 patients were included in the study. The mean age of these patients was 54 (18-91) years and 85 (78%) patients were females. A total of 48 patients (44.0%) had JAK2 mutation, six (5.5%) had CALR mutation, and one (0.9%) had MPL mutation. It was observed that there was a significant difference between the two groups in terms of gender, mean age, and hemoglobin value. While 87% of patients with triple-negative ET were females, this rate was 69% in patients with mutation-positive ET (p = 0.036). The mean age was 41.8 years in triple-negative ET and 67.1 years in patients with mutation-positive ET (p = 0.0001). While the mean hemoglobin value was 12.9 g/dl in patients with triple-negative ET, it was 14.4 g/dl in patients with mutation-positive ET (p = 0.0001). Conclusion It has been observed that ET with JAK2, CALR, or MPL mutations may have different phenotypic features compared to triple-negative ET, resulting in a clinical condition consisting of older patients with a higher erythrocyte count.

Extracorporeal photopheresis in steroid-refractory chronic graft-versus-host disease: A retrospective multicenter study.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) is a treatment strategy in steroid-refractory chronic graft-versus-host disease (cGvHD). In this study, we aimed to share our multicenter experience using ECP in our steroid-refractory cGvHD patients. MATERIALS AND METHODS: In this multicenter observational retrospective study with the participation of four Turkish transplant centers, 100 patients with the diagnosis of steroid-refractory cGvHD who underwent ECP were analyzed. All ECP procedures were performed with the off-line system. RESULTS: Severe cGvHD was observed in 77 % of the patients. 50 % of the patients had more than 1 organ involvement. The overall response rate in cGvHD was 58 %, and the complete response (CR) rate was 35 %. The skin was the most involved organ, with a response rate of 61.2 % (CR rate 30.6 %) in cGvHD. At a median 13 months (1-261) follow-up, overall survival (OS) was 41 % (n = 41) and the mortality rate was 59 % (n = 59). Median overall survival (OS) was 2 months for non-responders and 91 months for responders (p < 0.001). Significant OS differences were observed for patients responding to ECP in cGvHD (HR = 4.1, p = 0.001) patients. CONCLUSIONS: ECP is a good therapeutic alternative and could be used earlier in patients with steroid-resistant cGvHD.

Extracorporeal photopheresis in the treatment of acute graft-versus-host disease: A multicenter experience.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) is one of the second-line treatment strategies in steroid-refractory acute graft-versus-host disease (aGvHD). We aimed to share our multicenter experience using ECP in our steroid-refractory aGvHD patients. MATERIALS AND METHODS: A retrospective observational series of 75 aGvHD patients from 4 transplant centers were analyzed. All ECP procedures were performed with the off-line system. All patients received ECP as second-line therapy. RESULTS: 74.7 % of aGvHD patients were grade 3 or 4. The overall response rate was 42.7 % (32/75) in aGvHD including 17 complete responses (22.7 %). Median follow-up was 6 months (range, 1-68). Median overall survival (OS) was 5 months for non-responders and 68 months for responders (p < 0.001). Twenty-seven (36 %) patients are alive, and 48 (64 %) patients have died. CONCLUSIONS: Early initiated ECP could be an effective treatment alternative in patients with steroid-refractory aGvHD.

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.

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.

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.

A multiple myeloma patient who developed ischemic colitis during lenalidomide treatment: A rare case report.

INTRODUCTION: Multiple myeloma is a malignant neoplasm of plasma cells. Lenalidomide-dexamethasone treatment is a common treatment regimen used in refractory multiple myeloma. CASE REPORT: We describe the case of a 58-year-old male multiple myeloma patient with a history of relapse after six months of autologous stem cell transplantation. The patient had nausea and bloody diarrhea developed during lenalidomide treatment.Management and outcome: Computed tomography showed diffuse marked edematous thickness in the wall of colonic, hepatic and splenic flexure, transverse colon, descending colon and sigmoid colon. Colonoscopic observation revealed highly granular, hyperemic and fragile mucosa. Colon biopsy was consistent with ischemic colitis. Lenalidomide treatment was discontinued. One month later, colon findings were detected as normalized through a colonoscopy. DISCUSSION: Risk of developing ischemic colitis should be kept in mind in patients receiving lenalidomide which should be discontinued in cases with severe bloody diarrhea of unknown origin.

Impact of Guideline-Driven Approach in Follow-Up of Long-Term Complications After Allogeneic Hematopoietic Cell Transplant: Single Center Experience.

OBJECTIVES: After allogeneic stem cell transplant, patients may experience psychiatric, endocrinologic, pulmonary, and cardiovascular problems, as well as secondary malignancies and chronic graft-versus-host disease over the long-term follow-up. These long-term complications not only increase mortality and morbidity of transplant survivors but also decrease their quality of life. In this study, we shared our experiences with our guideline-driven approach for follow-up of long-term complications. MATERIALS AND METHODS: Our study included 91 patients who received allogeneic hematopoietic cell transplant between July 2009 and March 2016 at our medical center. In accordance with the current guidelines, a screening program was applied to all patients seen between February 2016 and February 2017. RESULTS: Median posttransplant follow-up duration was 36 months (range, 12-84 mo), and the median follow-up duration after initial diagnosis was 51 months (range, 15-109 mo). Evaluations of patients posttransplant showed ocular complications (50.6% of patients), oral complications (15.4%), respiratory complications (8.8%), cardiac complications (5.5%), metabolic syndrome (37.4%), liver complications (2.2%), skeletal complications (66.7%), endocrine complications (12.1%), secondary cancers (2.2%), psychosocial adjustment (27.7%), hypertension (5.5%), and type 2 diabetes mellitus (8.8%). CONCLUSIONS: For long-term follow-up, detailed evaluations of body organs and systems are essential. Early recognition of the aforementioned complications could decrease mortality and morbidity. For patients to be monitored by transplant centers over many years, training and awareness should be provided to ensure adequate follow-up of patients. Based on our results, we believe that the long-term follow-up guidelines used in our clinic are applicable to others.

Impacts of post-transplantation cyclophosphamide treatment after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Post-transplant cyclophosphamide has become a promising medical option after allogeneic HSCT. In this study we aimed to evaluate the efficacy of cyclophosphamide and cyclosporine combination in acute and chronic graft-versus-host disease (GvHD) prophylaxis in acute myeloid leukemia (AML) cases scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective analysis of data from 40 cases who underwent allogeneic HSCT under GvHD prophylaxis with cyclophosphamide and cyclosporine combination between April 2016 and August 2017 was made. Cyclophosphamide was given at daily doses of 50 mg/kg on post-transplant 3rd and 4th days, and cyclosporine was applied at daily doses of 3 mg/kg/day starting from the 5th post-transplant day. Cyclosporine dose was tapered beginning from the 45th postoperative day and completely discontinued on the 90th post-transplant day. Mean age was 38.25 ± 15.25 years. Posttransplant median follow-up was six months (6-17 months). Post-transplant, the number of deaths and mortality rates related and unrelated to transplantation were 5 (12.5%), and 2 (5%), respectively. Acute GvHD was diagnosed in 7 cases (17.5%), and relapse was noted in 9 cases (22.5%). Myeloablative or reduced intensity conditioning was performed in 22 (55%) and 18 (45%) patients, respectively. The distribution of the donors was as follows: match-related (n = 26; 65%), match-unrelated (n = 9, 22.5%) and haploidentical donors (n = 5; 12.5%). There was no statistically significant correlation between the transplant-related and unrelated mortality and parameters under investigation.Cyclophosphamide use appears to be a highly effective and promising strategy for acute GvHD prophylaxis in non-haploidentical allogeneic HSCT cases. Identification of the impact of cyclophosphamide use on the development of chronic GvHD needs further investigation.