Concurrent congenital hemophilia B and acquired hemophilia A: a unique case report.

Congenital hemophilia B is a rare X-linked recessive bleeding disorder caused by factor IX deficiency. Acquired hemophilia A is a rare, acquired bleeding disorder that presents with new-onset bleeding, especially in older adults, due to the development of auto-antibodies against factor VIII (FVIII). This case report presents the medical management of a patient with congenital hemophilia B and acquired hemophilia A. We highlight the limitations of maintaining factor levels with factor replacement therapy alone, particularly in hemophilia patients who have developed factor inhibitors. In addition, we draw attention to the need for dose escalation, the cost, and the need for immune-tolerance induction therapy. This case illustrates that when the current diagnosis does not explain the full clinical picture and laboratory data are inadequate, it is important to continue to seek alternative diagnoses and cost-effective treatment.

Management of Primary Immune Thrombocytopenia - Turkish Modified Delphi-Based Consensus Statement for Special Considerations.

Introduction: Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with complex and unclear mechanism of increased immune distruction or impaired production of platelets. While management of ITP is evolving, there is a need for guidance particularly in certain circumstances such as pregnancy, emergency and for patients requiring co-medications. We aimed to determine the tendencies of hematologists in Turkiye on such special conditions. Methods: As a modified Delphi method, Turkish National ITP Working Group founded under Turkish Society of Hematology developed a questionnaire consisting of statements regarding pregnancy, emergency and circumstances regarding co-treatment with antiaggregant or anticoagulants. 107 Hematologists working either in university or state hospitals voted for their agreement or disagreement of the statements for two consequential rounds. Results: Participant hematologists reached an agreement on the starting treatment in pregnant patients with platelets less than 30 x109/L and delivery of either normal or cesarian section to be safely performed above 50 x109/L. For emergency and rescue management of ITP, our panel have agreed against the use of high dose corticosteroids alone, preferred a combination with transfusion or IVIG. For patients who require interventions, platelet counts >50 x109/L were regarded as safe for low risk procedures as well as co-treatment with antiplatelets or anticoagulants. Conclusion: As National ITP study group, we have observed the need to increase the practice guidance in patients with primary ITP requiring additional treatments including invasive interventions, and co-treatments towards coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a certain lack of consensus on the thresholds of platelet counts as well as co-morbidities and co-medications. This lack of consensus may be due to the variations in the practices.

Baseline Characteristics of a Patient Cohort and Predictors of In-hospital MORtality in CORonary Care Units (MORCOR-TURK) Trial in Türkiye.

OBJECTIVE: The MORtality in CORonary Care Units in Türkiye (MORCOR-TURK) trial is a national registry evaluating predictors and rates of in-hospital mortality in coronary care unit (CCU) patients in Türkiye. This report describes the baseline demographic characteristics of patients recruited for the MORCOR-TURK trial. METHODS: The study is a multicenter, cross-sectional, prospective national registry that included 50 centers capable of 24-hour CCU service, selected from all seven geographic regions of Türkiye. All consecutive patients admitted to CCUs with cardiovascular emergencies between September 1-30, 2022, were prospectively enrolled. Baseline demographic characteristics, admission diagnoses, laboratory data, and cardiovascular risk factors were recorded. RESULTS: A total of 3,157 patients with a mean age of 65 years (range: 56-73) and 2,087 (66.1%) males were included in the analysis. Patients with arterial hypertension [1,864 patients (59%)], diabetes mellitus (DM) [1,184 (37.5%)], hyperlipidemia [1,120 (35.5%)], and smoking [1,093 (34.6%)] were noted. Non-ST elevation myocardial infarction (NSTEMI) was the leading cause of admission [1,187 patients (37.6%)], followed by ST elevation myocardial infarction (STEMI) in 742 patients (23.5%). Other frequent diagnoses included decompensated heart failure (HF) [339 patients (10.7%)] and arrhythmia [272 patients (8.6%)], respectively. Atrial fibrillation (AF) was the most common pathological rhythm [442 patients (14%)], and chest pain was the most common primary complaint [2,173 patients (68.8%)]. CONCLUSION: The most common admission diagnosis was acute coronary syndrome (ACS), particularly NSTEMI. Hypertension and DM were found to be the two leading risk factors, and AF was the most commonly seen pathological rhythm in all hospitalized patients. These findings may be useful in understanding the characteristics of patients admitted to CCUs and thus in taking precautions to decrease CCU admissions.

Management of Adult Primary Immune Thrombocytopenia: Delphi-Based Consensus Recommendations

Objective: Primary immune thrombocytopenia (pITP) is an acquired autoimmune disorder related to the increased destruction and/or impaired production of platelets. Its diagnosis and management are challenging and require expertise and the interpretation of international consensus reports and guidelines with national variations in availability. We aimed to assess the agreement of hematologists in Türkiye on certain aspects of both first-line and second-line management of patients with pITP. Materials and Methods: Applying a modified Delphi method, the Turkish National ITP Working Group (14 steering committee members), founded under the auspices of the Turkish Society of Hematology, developed a 21-item questionnaire consisting of statements regarding the first-line and second-line treatment of pITP. A total of 107 adult hematologists working in either university or state hospitals voted for their agreement or disagreement with the statements in two consecutive rounds. Results: The participants reached consensus on the use of corticosteroids as first-line treatment and with limited duration. Methylprednisolone was the corticosteroid of choice rather than dexamethasone. Use of intravenous immunoglobulin was not preferred for patients without bleeding. It was also agreed that thrombopoietin receptor antagonists (TPO-RAs) or rituximab should be recommended as second-line treatment and that splenectomy could be considered 12-24 months after diagnosis in patients with chronic pITP. Conclusion: The optimization of the dose and duration of TPO-RAs in addition to corticosteroids is necessary to improve the management of patients with pITP.

The effect of thrombocytapheresis on hemogram and biochemistry parameters in patients with essential thrombocytemia.

BACKGROUND: Essential thrombocythemia is one of the chronic myeloproliferative neoplasms characterized by clonal proliferation of myeloid cells with variable morphological maturation and hematopoietic activity.It is characterized by excessive clonal platelet production with a tendency to thrombosis and bleeding. Thrombocytapheresis is the removal of platelets by apheresis techniques. Thrombocytapheresis is generally recommended in patients with essential thrombocythemia with acute, severe thrombotic or hemorrhagic events. METHODS: The study included 39 patients who were diagnosed with essential thrombocythemia, started cytoreductive and aspirin therapy, and underwent thrombocytapheresis due to the development of acute severe thrombotic or hemorrhagic events, diagnosed in the adult hematology clinic of Inönü University Turgut Ozal Medical Center. Hemogram and biochemistry values of the patients were scanned retrospectively. RESULTS: After thrombocytapheresis, a statistically significant difference was found between the first and last measurements of hemoglobin, mean platelet volume, White blood cell, neutrophil, platelet, platelet distribution width, creatine, lactate dehydrogenase, fibronogen and calcium levels of the patients. CONCLUSION: The use of thrombocytapheresis in patients with essential thrombocytosis causes a rapid decrease in platelet values as well as an effect on hemogram and biochemistry parameters. Other hemogram and biochemistry parameters such as platelet value should be monitored in patients.

Effect of extracorporeal photopheresis on survival in acute graft versus host disease.

BACKGROUND: Extracorporeal photopheresis (ECP) is the main non-pharmacological approach accompanying systemic medical treatments in steroid-resistant acute or chronic graft versus host disease. The study aimed to examine the effect of ECP on survival in acute graft versus host disease (aGVHD). METHODS: A total of 35 patients who were followed up in the adult hematology clinic of Inönü University Turgut Özal Medical Center for aGVHD were included in the study. Stem cell transplantation and ECP application parameters that may affect the survival of the patients were examined. RESULTS: In aGVHD using ECP, the degree of involvement affects survival. Involvements with a clinical and laboratory score (Glucksberg system) of 2 and above significantly reduced survival. The duration of ECP use is associated with survival. Especially, 45 days and longer use increases survival (hazard ratio, P-value <.05). The duration of steroid use was found to be effective in survival in aGVHD (P < .001). ECP administration day (P = .003), duration of steroid use (P < .001), duration of ECP use (P = .001), and grade of aGVHD (P < .001) affect survival. CONCLUSION: ECP use is effective in survival in patients with aGVHD score ≥2. In patients with aGVHD, especially the use of 45 days and longer has a positive effect on survival. The duration of steroid use is associated with survival in aGVHD.

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.

Does ferritin level affect the outcomes of autologous stem cell transplantation equally in all diseases?

BACKGROUND: In this retrospective study, we evaluated the effect of ferritin levels on the outcomes of autologous stem cell transplantation in patients with MM or lymphoma. METHODS: In this study, 170 patients with measured ferritin levels within one month before transplantation who underwent ASCT with the diagnosis of MM or lymphoma were evaluated. The cut-off value of ferritin was determined as 500 ng/mL to evaluate the transplant outcomes in both groups. The hematological recovery status/duration, febrile neutropenia rate, hospitalization time, transplant-related mortality (TRM) in the first 100 days, and OS were evaluated according to the ferritin level RESULTS: Of all patients, 105 (61,8%) were diagnosed with MM and 65 (38.2%) with lymphoma. Ferritin levels had no statistically significant effect on the engraftment status/times, the febrile neutropenia rates, and hospitalization times of both lymphoma and myeloma patients (p > .05). Ferritin level was not significantly associated with TRM in MM (p = .224). However, in lymphoma, ferritin level was significantly associated with TRM (33.3% for ferritin level ≥500 ng/L vs. 5.3% for ferritin level ng/mL, p = .005). There was no statistically significant correlation between ferritin value and OS in MM group [ferritin level ≥ 500 ng/L: 39.9 months (95% CI: 33.7-46.1) and ferritin level 500 ng/mL: 39.4 months (95% CI: 36.5-42.2), p = .446]. Ferritin level was significantly associated with OS in patients with lymphoma [ferritin level ≥ 500 ng/L: 22.1 months 95% CI: 14.7-29.5), ferritin level 500 ng/mL: 27.3 months (95% CI: 22.4-32.2), p = .038] CONCLUSION: High ferritin level is important prognostic factor on survival after ASCT in patients with lymphoma.

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.

The effect of G-CSF used after allogeneic hematopoietic stem cell transplantation on engraftment times and platelet suspension replacement numbers.

BACKGROUND: With the use of granulocyte colony stimulating factor (G-CSF) after allogeneic hematopoietic stem cell transplantation (HSCT), the duration of neutrophil engraftment and hospitalization were shortened. However, there is no consensus on the effect of G-CSF on platelet engraftment time. The primary aim of our study is to determine the effect of G-CSF use on platelet engraftment time after HSCT. Secondary purposes are to determine the number of platelet suspension, number of erythrocyte suspension and incidence of acute graft versus disease after HSCT. MATERIAL AND METHODS: Patients who had allogeneic stem cell transplantation at our center between 01.01.2011 and 01.01.2022 were retrospectively analyzed. Patients were divided into 2 groups as those who received and did not receive G-CSF after transplantation. RESULTS: A total of 64 patients were included. While 32 patients were given post-HSCT G-CSF support, the other 32 patients were not given. Neutrophil engraftment time and length of hospital stay were shorter in the group receiving G-CSF (p < 0.05). Platelet engraftment time was shorter in the group that did not receive G-CSF (p < 0.05). The incidence of acute GVHD of the patients in group 1 tended to be higher than the patients in group 2 (40.6 % vs 15.6 %, p = 0.052). Post-HSCT platelet suspension was less in the group that did not receive G-CSF, but this difference was not statistically significant (p = 0.173). CONCLUSION: While the positive effect of post HSCT G-CSF use on duration of neutrophil engraftment and hospitalization is evident, its effects on platelet engraftment need to be investigated.

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients.

OBJECTIVE: In this study, we aimed to report the effectiveness of hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT). MATERIAL AND METHODS: The data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed. RESULTS: Neutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001). CONCLUSION: HCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.

Early therapeutic plasma exchange may improve treatment outcomes in severe acute toxic Hepatitis.

BACKGROUND AND OBJECTIVES: Acute toxic hepatitis can result in a different clinical course from a completely curable disease to subacute hepatitis, chronic hepatitis, and fulminant hepatitis failure, which is quite mortal. For this purpose, therapeutic plasma exchange (TPE) can be used for improving treatment outcomes by reducing the harmful substances caused with and/or without liver function in acute toxic hepatitis. We aimed to evaluate treatment outcomes in severe acute toxic hepatitis patients who applied early TPE procedure. MATERIALS AND METHODS: A total of 335 patients who received TPE between 2010-2021 were retrospectively screened and 59 (male/female, 30/29; min/max-age, 22-84) patients with acute toxic hepatitis who underwent TPE in the first 24 h were included in the study. TPE was performed in patients who had high total bilirubin level (>10 mg/dL). Laboratory parameters of the patients before and after the TPE procedure, number of patients developed complications of acute toxic hepatitis and mortality rates were evaluated for effectiveness of TPE. RESULTS: Acute toxic hepatitis was associated with hepatotoxic drugs in 44 (74.5 %), herbal medication 6 (10.2 %), mushroom poisoning 6 (10.2 %) and with substance abuse 3 (5.1 %) in patients. When the patients were compared based on INR, liver function tests, ammonia, lactate and Model For End-Stage Liver Disease (MELD) score at baseline, 48 h after TPE (independently of TPE number) and before final state a statistically significant decrease was observed in all parameters (p < 0.05). Fifty three (90 %) of patients improved without complications, the remaining 6 (10 %) patients were diagnosed with fulminant hepatitis. All these remaining patients died before liver transplantation (LTx) could be performed. CONCLUSION: TPE is a safe, tolerable therapy option and early TPE may improve treatment outcomes in severe acute toxic hepatitis.

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.

The effect of therapeutic plasma exchange on management of HELLP Syndrome: The report of 47 patients.

BACKGROUND AND OBJECTIVES: HELLP syndrome is a life-threatening condition that may potentially cause complications during pregnancy. If not diagnosed and treated quickly, HELLP syndrome may lead to serious complications both for the mother and the baby. The aim of this study was to determin the effectiveness of therapeutic plasma exchange (TPE) for treatment of Class-I HELLP syndrome. MATERIALS AND METHODS: Laboratory results from 47 patients with Class-I HELLP syndrome patients who underwent TPE between 2011 and 2020 were recorded before and after the procedure. A central venous catheter was inserted, and TPE was performed in patients who had not responded to delivery, steroid, and supportive therapy (blood products, anti-hypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. RESULTS: The average age of patients was 33 ± 4.7 years (range; 21-39 years). A mean of 5 (range; 4 to 6) TPE sessions were performed. There was a statistically significant decrease in total bilirubin, lactic dehydrogenase, aspartate aminotransferase, and alanine aminotransferase levels in all patients, whereas a significant increase in platelet count was observed (p < 0.05). Furthermore, clinical and laboratory improvement was achieved. CONCLUSION: In all patients with HELLP syndrome, a dramatically clinical and laboratory improvement occurred after TPE. Our study suggests that postpartum use of TPE within 24 hours is an efficient treatment option for Class-I HELLP syndrome.

Selection of the mobilization regimen in lymphoma patients: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Consolidation with autologous stem cell transplantation (ASCT) is recommended for patients with recurrent or refractory lymphoma after salvage chemotherapy. Stem cells which will be used in ASCT are provided by mobilization using granulocyte colony stimulation factor (G-CSF) or chemotherapy plus G-CSF. The aim of this study was to compare the effect of various mobilization regimens on the clinical parameters of lymphoma patients. MATERIALS AND METHODS: Mobilization interventions of lymphoma patients were analysed retrospectively. The patients were divided into 3 groups according to the mobilization method implemented to collect stem cells before ASCT, (Group 1: Salvage chemotherapy plus G-CSF, Group 2: Cyclophosphamide plus G-CSF, Group 3: G-CSF alone). RESULTS: Analysis of CD34+ cell counts of the 3 groups revealed a significant difference (p < 0.001). Although the number of CD34+ cells collected were different, the neutrophil and platelet engraftment of the 3 groups were similar (p > 0.05). Furthermore, the results were similar in the separate analysis of NHL and HL patients. While the mobilization success rate in group 1 was 97.8 %, it was 90.2 % in group 3. This difference showed a certain trend towards statistical significance (p = 0.074). Patients who received DHAP plus G-CSF had a higher CD34+ count, while neutrophil engraftment was shorter than with ESHAP plus G-CSF (p < 0.05). CONCLUSION: Although the success rate of mobilization and number of CD34+ cell collected were higher in the salvage chemotherapy plus G-CSF than G-CSF alone, G-CSF alone group provided similar neutrophil and thrombocyte engraftment in most lymphoma patients.

An innovation in stem cell harvesting: Heparin use.

BACKGROUND AND OBJECTIVES: Stem cell transplantation is a growing treatment strategy for most malignant and non- malignant hematological diseases. Plerixafor and granulocyte colony stimulating factor (G-CSF) are usually used in mobilization regimens to increase the CD34+ cell count in the harvest. Heparin is a sulphated glycosaminoglycated polymer with 12-15 kDa mass. Heparin inhibits the CXCR4/SDF1 axis, as does plerixafor. In this study, our aim was to investigate the effect of using heparin on stem cell mobilization and harvesting. MATERIALS AND METHODS: We administered 5000 units of unfractioned heparin intravenously in 150 mL (mL) of isotonic sodium chloride solution, 15 min before the stem cell harvesting procedure to 141 patients who underwent bone marrow transplantation between the years of 2018 and 2019 at our Stem Cell Transplantation Unit. Thirty patients were included as a control group, and they were not given heparin. The study population included patients with multiple myeloma and lymphoma equally in each group. RESULTS: In all patients hematopoeitic stem cells were successfully harvested in a single cycle of apheresis. In multiple myeloma patients who received heparin, the mean collected CD34+ cell number was 8 × 106/kg, and the mean CD34+ cell number yield was 12,555/µl. In the control group, the mean collected CD34+ cell number was 4,2 × 106/kg, and mean CD34+ cell number in yield was 492/µl. In lymphoma patients who received heparin, the mean collected CD34+ cell number was 6,8 × 106/kg, and the mean CD34+ cell number was 1421/µl. In the control group the mean collected CD34+ cell number was 4,3 × 106/kg, and the mean CD34+ cell number was 358/µl. The effect of heparin on the collected stem cell number in both myeloma and lymphoma patients was statistically significant (p < 0.01). CONCLUSIONS: Our results have shown that heparin increases harvested stem cell numbers significantly. Heparin may be a promising agent for stem cell harvesting.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.