The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

Stem cell mobilizating effect of heparin in patients undergoing autologous stem cell transplantation.

BACKGROUND: Adequate stem cell collection is essential for successful stem cell transplantation. Heparin enhances stem cell mobilization by competing with heparin sulfate proteoglycans. Heparin is also used as an anticoagulant before leukapheresis. Here, we evaluated the effects of heparin on stem cell mobilization in patients who underwent autologous stem cell transplantation (ASCT). METHODS: We evaluated patients who underwent ASCT. Patients were divided into two groups: those who received heparin plus citrate (heparinized patients) and those who received citrate only (nonheparinized patients) for anticoagulation. Univariate and multivariate analyses were also performed. The collection efficiency 2 (CE2) for CD34+ cells was calculated and compared between heparinized and nonheparinized patients. RESULTS: This study included 1017 patients. There were 478 (47%) heparinized and 539 (53%) nonheparinized patients. The number of collected CD34+ cells was significantly higher in heparinized patients (P < .00001). The multivariate analyses showed that using heparin was an independent positive factor for collected CD34+ cells (adj-R2 = 0.744; F = 369.331, P < .00001). CE2 was significantly higher in heparinized patients than in nonheparinized patients (66.8% vs 52.1%; P < .00001). The rate of collecting at least 2 × 106 /kg CD34+ cells was 3.3 times higher for heparinized patients in poor mobilizers (P < .00001). Heparinized patients had significantly higher total nucleated and mononuclear cell counts (P < .00001 and <.00001, respectively). CONCLUSION: Heparin enhances stem cell collection and increases CE2. The use of heparin may reduce the need for other strategies to increase stem cell mobilization.

Unmet clinical needs and challenges in the management of acute leukemia in Turkey: a modified Delphi study.

Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient-physician communication in acute leukemia (AL). Materials & methods: The study was based on a modified Delphi approach. A questionnaire including the major potential obstacles was circulated twice among 13 hematologists. Results: The obstacles in AL management were limited access to the novel treatments and genetic tests, limited bed capacity, insufficient level of knowledge among allied health personnel, limited availability of psycho-oncological support and low levels of awareness in the population about the importance of stem cell donation. Conclusion: The challenges in the management of AL are critical to guide the efforts to improve the quality of healthcare delivery and the evidence-based decision making at treatment of AL patients.

Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry.

Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Allogeneic Hematopoietic Stem Cell Transplantation for Primary Myelofibrosis: A 20-year Experience in a Single Center

Background: Allogeneic hematopoietic stem cell transplantation is a well-established approach for patients diagnosed with primary myelofibrosis and remains the only potentially curative treatment. Aims: To present the overall outcome of patients with myelofibrosis treated with allogeneic hematopoietic stem cell transplantation. Study Design: A retrospective cross-sectional study. Methods: This study is a retrospective analysis of 26 consecutive patients with primary myelofibrosis who underwent transplantation at our center between January 2002 and January 2022. Disease and transplant variables contributing to outcomes were analyzed. Results: The median age at the time of transplantation was 52.5 (range, 32-63) years and the median time from diagnosis to allogeneic hematopoietic stem cell transplantation was 25 (range, 3.1-156.8) months. Myeloablative conditioning and reduced-intensity conditioning regimens were used in 8 (30.8%) and 18 (69.2%) transplantations, respectively. Neutrophil and platelet engraftment was achieved in 23 patients at a median follow-up of 21.2 months (range, 12 days to 234.8 months). Primary graft failure occurred in 1 of 23 patients (4.3%). Neutrophil and platelet engraftment occurred at a median of 16 (range, 12-39) days and 20 (range, 11-78) days, respectively. Acute graft-versus-host disease was seen in 11 of 22 patients engrafted allografts, of which 7 (31.8%) were grade 3-4 acute graft-versus-host disease. Eight patients (36.4%) developed chronic graft-versus-host disease, and three cases were extensive. Four patients (19%) relapsed after a median of 5.5 months, and three patients received donor lymphocyte infusion. The 3-year overall survival rate of the entire study population was 46.2%. The median overall survival was not reached in the myeloablative conditioning group; however, it was 11.9 months in the reduced-intensity conditioning group (p =0.3). According to the donor graft source, the median overall survival was 0.73 months in mismatched unrelated graft recipients, 12 months in matched sibling donors, and not reached in matched unrelated graft recipients (p = 0.03). The 3-year progression-free survival rate of patients who survived > 100 days was 74.7%. The effect of JAK-2 status, graft source, conditioning regimen or dynamic international prognostic scoring system on progression-free survival was not statistically significant. Conclusion: Given the poor prognosis of non-transplant recipients and the lack of non-transplant curative approaches, our results support the consideration of allogeneic hematopoietic stem cell transplantation for eligible patients with primary myelofibrosis.

Generic Lenalidomide Rivelime Versus Brand-name Revlimid® in the Treatment of Relapsed/Refractory Multiple Myeloma: A Retrospective Single-center Experience on Efficacy, Safety and Survival Outcome.

BACKGROUND: This study aimed to compare use of original brand-name lenalidomide (Revlimid®) vs. generic equivalent (Rivelime®) in terms of efficacy, safety and survival outcome in patients with relapsed/refractory multiple myeloma (RRMM) PATIENTS AND METHODS: A total of 184 patients RRMM (median age: 62 years, 60.9% were males) who received singlet, doublet or triplet lenalidomide-containing regimens including either Revlimid® (n=74) or Rivelime® (n=110) were included in this study. Treatment response was based on evaluation of objective response to treatment (ORR) including the sum of patients who achieved partial response (PR), very good partial responses (VGPR) or complete response (CR) to therapy. Progression-free survival (PFS), overall survival (OS) and safety data were also recorded. RESULTS: Revlimid® and Rivelime® groups were similar in terms of ORR (54.1 vs. 60.0%), CR (22.5 vs. 28.8%), VGPR (55.0 vs. 50.0%) and PR (22.5 vs. 21.2%) rates. Median (SE) PFS time were similar between Rivelime® vs. Revlimid® treated patients who were in the 2nd line (30.3(3.8) vs. 22.7(7.0) months, p=0.827) or 3rd line of therapy (38.1(12.1) vs. 20.1(0.9) months, p=0.147) at lenalidomide initiation. Two groups also had similar OS rate (83.8 vs. 73.6%) and OS time (mean 122.3 vs. 123.5 months). Side effects were manageable in both groups. CONCLUSION: In conclusion, replacing Revlimid® with its generic version Rivelime® in singlet, doublet or triplet lenalidomide containing RRMM regimens seems not to compromise the efficacy of treatment, and to yield a similarly improved response rates and survival outcome and no additional toxic effects, enabling a long-term therapy.

Eltrombopag for the Treatment of Poor Graft Function Following Haematopoietic Cell Transplantation: Real-Life Data

Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre's experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x109/l (1-23), which increased to 41x109/l (6-150). The median platelet count increment was 29.5x109/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x109/l (0.39-5.1), which increased to 2.35 x109/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Effect of CD34⁺ Total/Myeloid CD34⁺ Cell Progenitors and B-Lymphoid Progenitors Within the Bone Marrow Grafts on the Hematopoietic Recovery After Hematopoietic Stem Cell Transplantation.

OBJECTIVES: The influence of CD34⁺ cells on transplant outcomes following hematopoietic stem cell transplantation remains controversial. A minimum of 2.0 to 2.5 million CD34⁺ cells/kg of patient weight is requested for a rapid and durable engraftment. The aim of this study was to detect the ratio of CD34+ B-lymphoid progenitors (hematogones) in bone marrow grafts and investigate their effects on hematopoietic recovery after transplant. MATERIALS AND METHODS: Our study included 41 patients who received a bone marrow graft from their HLA-matched donor from 2016 through 2019. The CD34⁺ cell numbers within the graft were detected using Stem-Kit (Beckman Coulter). The ratio of CD34⁺ hematogones was determined either by their light scatter characteristics or by the detection of CD34, CD19, or CD10 coexpressing cells in a separate tube. RESULTS: The median number of CD34⁺ cells was 5.9 × 106/kg (0.8-14.3 × 106/kg). The CD34⁺ cells consisted of 71% (range, 35.7%-100%) and 29% (range, 5.7%-64.3%) myeloid and B-lymphoid progenitors, respectively. Percentage of CD34⁺ (P < .001) and total (P < .001) hematogones in correlation with donor age. Time of neutrophil engraftment was significantly longer (P = .039) when total infused CD34⁺ cell content was <3 × 106/kg. CONCLUSIONS: A remarkable population of hematogones within the CD34⁺ cell pool was detected in bone marrow grafts. Detection of the ratio of hematogones and most primitive stem cells (CD34⁺CD90⁺CD38⁻) may overall provide more information to build a better correlation between CD34⁺ cell content and the recovery of bone marrow.

Turkey real-life data: demographic features, treatment results and effects of comorbidities in chronic myeloid leukemia.

Aim: This study aimed to identify patient characteristics, treatment patterns and outcomes and to evaluate the effects of presence of comorbidities at diagnosis in chronic phase (CP)-chronic myeloid leukemia (CML) patients in Turkey. Materials & methods: Hospital records between 2005 and 2018 were retrospectively reviewed. Results: Of 861 CP-CML patients included, 31% had at least one comorbidity at diagnosis. Sex, cardiovascular disease status at diagnosis and molecular (at least major) and cytogenetic (partial and complete) responses were the independent predictors of survival. Conclusion: The response rates of CP-CML patients to the tyrosine kinase inhibitors were satisfactory. In addition to tolerability and side effect profiles of drugs, comorbidity status of patients should also be considered in treatment choice in CML patients.

This study aimed to identify patient characteristics, treatment patterns and outcomes and to evaluate the effects of presence of comorbidities at diagnosis in chronic phase (CP)-chronic myeloid leukemia (CML) patients in Turkey. Hospital records of patients between 2005 and 2018 were retrospectively reviewed. Of the included 861 CP-CML patients, 31% had at least one comorbidity at diagnosis. The survival of the patients was affected by sex, cardiovascular disease status at diagnosis, and molecular (at least major) and cytogenetic (partial and complete) responses. The response rates of CP-CML patients to the tyrosine kinase inhibitors were satisfactory. In addition to tolerability and side effect profiles of drugs, comorbidity status of patients should also be considered in treatment choice in CML patients.

Gemcitabine, Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients.

BACKGROUND: Second line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. PATIENTS AND METHODS: Forty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. RESULTS: Thirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. CONCLUSION: Our results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.

Alpha-1-Antitrypsin Experience for Steroid-Resistant Acute Graft-Versus-Host Disease.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) treatment has a low response rate and a high risk of infection in allogeneic hematopoietic stem cell transplantation. The standard approach to be applied in this situation is uncertain. This study aims to evaluate the effectiveness and safety of alpha-1-antitrypsin (AAT). In the study, the results of five SR-aGVHD patients received AAT evaluated. Complete response was seen 2 of four patients with gastrointestinal (GI) aGVHD, partial response in one GI and one liver aGVHD. The overall response rate was 80%. AAT is an effective and safe treatment option in SR-aGVHD.

The effect of comorbidities on the choice of tyrosine kinase inhibitors in patients with chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) approved for chronic myeloid leukemia known to have similar efficacies but different safety profiles. Therefore, the choice of patient-specific treatments is driven by factors such as tolerability and adverse event profile of TKIs. This review article examines the most up-to-date data and provides practical recommendations for clinical approaches. Nilotinib and ponatinib should be avoided in patients with cardiovascular risk factors, dasatinib in patients with lung damage and bosutinib and nilotinib in patients with liver disease. Considering that certain comorbidities predispose some patients to developing severe adverse events when receiving TKIs, the first- and second-line treatment of chronic myeloid leukemia should be tailored to each patient's individual condition.

Pretransplant Consolidation Therapies Improve the Outcome of Myeloablative Allogeneic Transplantation in Adults with Ph-negative Acute Lymphoblastic Leukemia.

BACKROUND AND AIM: The benefit of pre-transplant consolidation in patients with acute lymphoblastic leukemia (ALL) who achieved first complete remission (CR1) has not yet been clearly demonstrated. Here, we aimed to investigate the relationship between the treatments received before transplantation and transplant outcome in Ph-ALL patients who underwent myeloablative allo-HSCT in CR1. PATIENTS AND METHODS: A total of 55, 32 (58.2%) men and 23 (41.8%) women, who underwent allo-HSCT with the diagnosis of Ph-ALL were evaluated retrospectively. All patients underwent to allo-HSCT with myeloablative conditioning regimen in the 1st CR from the available donor. RESULTS: In patients who received >2 consolidation, the 2-year and 3-year OS was 69% and 65%, respectively, while the 2-year and 3-year OS was 39% and 26%, respectively, in those who received < 2 consolidation (P =.03). RFS was similar in both groups (P = .8). One year- NRM was found 28% in patients who received ≥ 2 consolidations, and 37% in patients who received <2 consolidation (P =.06). L-asparaginase, high dose methotrexate, and cranial treatments given before transplantation had no effect on transplant outcomes (P > .05). CONCLUSION: Contrary to the belief that pre-transplant consolidation is not beneficial in ALL patients who proceed with allo-HCST in CR1, our results showed that consolidation treatments reduce NRM and improve the survival.

Lipoprotein apheresis efficacy and challenges: single center experience.

INTRODUCTION: Lipoprotein apheresis (LA) is an extracorporeal therapy which removes apolipoprotein B-containing particles from the circulation. We evaluated techniques and efficiency of lipoprotein apheresis procedures applied to patients with familial and non-familial hypercholesterolemia (FH) at our center. METHODS: We retrospectively evaluated 250 LA procedures applied to 27 patients with dyslipidemia between March 2011 and August 2019. RESULTS: A total of 27 patients, of whom 19 (70.4%) were male and 8 (29.6%), female, were included. Eighteen (66.7%), 6 (22.2%) and 3 (11.1%) patients were diagnosed with non-FH, homozygous FH (HoFH) and heterozygous FH (HeFH), respectively. Two different apheresis techniques, direct adsorption of lipoproteins (DALI) (48.8%) and double filtration plasmapheresis (DFPP) (51.2%), were used. The change in the serum total cholesterol (TC) level was the median 302 mg/dl (171-604 mg/dl) (60.4%) in HoFH patients, 305 mg/dl (194-393 mg/dl) (60.8%) in HeFH patients and 227 mg/dl (75-749 mg/dl) (65.3%) in non-FH patients. The change in the serum low-density lipoprotein (LDL) level was the median 275 mg/dl (109-519 mg/dl) (64.2%), 232 mg/dl (207-291 mg/dl) (64.5%) and 325 mg/dl (22-735 mg/dl) (70.9%) in patients with HoFH, HeFH and non-FH, respectively. A significantly effective reduction in serum lipid levels, including TC, LDL and triglycerides, was achieved in all patients, regardless of the technique, p < .001. The decrease in the serum TC and LDL levels was significantly higher in the DFPP, compared to the DALI, being 220 mg/dl (-300 to 771) vs 184 mg/dl (64-415), p < .001 and 196 mg/dl (11-712) vs 157 mg/dl (54-340), p < .001, respectively. CONCLUSIONS: Our results showed that LA is a highly effective treatment in reducing serum lipid levels and safe, without any major adverse event.

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA).

BACKGROUND: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. METHODS: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. RESULTS: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. CONCLUSIONS: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Leukemic stem cells shall be searched in the bone marrow before "tyrosine kinase inhibitor-discontinuation" in chronic myeloid leukemia.

BACKGROUND: Leukemic stem cells (LSCs) of chronic myeloid leukemia (CML), persisting in the bone marrow (BM) niche, could be responsible for the relapses within the patients of whom the treatment-free remission (TFR) had been attempted. We assessed the presence of the CML LSCs in the peripheral blood (PB) and concurrently in the BM in the patients with chronic-phase CML (CP CML). PATIENTS AND METHODS: Thirty-eight patients with CP CML were included into the study. CD45+ /CD34+ /CD38- cells with positive CD26 expression were considered as CML LSCs (CD26+ LSC) by using multiparameter flow cytometry (FCM). RESULTS: Mean BCR-ABL, PB LSC, and BM LSC were 58.528 IS (37.405-83.414 IS), 237.5 LSC/µL (16-737.5 LSC/µL), and 805 LSC/106  WBCs (134.6-2470 LSC/106  WBCs), respectively, in newly diagnosed CML patients. In the patients with BCR-ABL positive hematopoiesis, mean BCR-ABL, PB LSCs, and BM LSCs were 30.09 IS (0.024-147.690 IS), 13.5 LSC/µL (0-248.7 LSC/µL) and 143.5 LSC/106  WBCs (9-455.2 LSC/106  WBCs), respectively. No CML LSCs were detected in PB of patients who achieved deep molecular response (DMR). BM LSCs of the patients who were in DMR were 281.1 LSC/106  WBCs (3.1-613.7 LSC/106  WBCs). The amount of PB LSCs was highest in patients with newly diagnosed CML (P < .001). CONCLUSION: LSCs persisted in the BM of the patients with DMR, whereas there was no LSCs in the peripheral blood. The investigation of the CML LSCs in bone marrow before deciding TKI discontinuation could be justified to achieve and maintain stable TFR.