Assessment of Stem Cell Transplant Eligibility in Recipients with Oral Foci of Infection: Appropriate Conditioning Regimens.

OBJECTIVES: It is unclear whether patients with oral foci of infection should be approved for hematopoietic stem cell transplant with or without posttransplant cyclophosphamide. We compared the presence of oral foci of infection status on the effects of various conditioning regimens for such patients. MATERIALS AND METHODS: Three groups were classified as autologous (carmustine-etoposide-cytarabinemelphalan, mitoxantrone-melphalan, and melphalan 200 mg/m² groups; n = 502 patients), and 6 groups were classified as allogeneic (busulfan-fludarabinerabbit anti-T-lymphocyte globulin, busulfanfludarabine-posttransplant cyclophosphamide, fludarabine-cyclophosphamide-anti-T-lymphocyte globulin, busulfan-fludarabine-anti-T-lymphocyte globulin-posttransplant cyclophosphamide, total body irradiation-posttransplant cyclophosphamide, and other; n = 428 patients). Data were collected from a database that met international accreditation requirements. We evaluated dental radiological findings and calculated interobserver reliability. RESULTS: Oral foci of infections increased febrile neutropenia and bacterial infection frequencies in both groups but only increased mucositis frequency in patients with allogeneic treatment. The frequencies of oral foci of infection-related complications were similar in both the autologous and allogeneic groups. Rate of graft-versus-host disease was not affected by oral foci of infection status. Periodontitis/cysts and periapical lesions increased the risk of infections at day 100 in the mitoxantrone-melphalan group versus the melphalan 200 mg/m² group. We observed no differences among the autologous transplant groups in terms of early mortality. Similarly, no differences in early mortality were observed among the allogeneic groups. CONCLUSIONS: Transplant is a valid option in patients with oral foci of infections undergoing various autologous and allogeneic transplant protocols when time is of the essence, even at myeloablative dose intensities.

Comparison of the clinical course of COVID-19 infection in sickle cell disease patients with healthcare professionals.

It is highly expected that COVID-19 infection will have devastating consequences in sickle cell disease (SCD) patients due to endothelial activation and decreased tissue and organ reserve as a result of microvascular ischemia and continuous inflammation. In this study, we aimed to compare the clinical course of COVID-19 in adult SCD patients under the organ injury mitigation and clinical care improvement program (BASCARE) with healthcare professionals without significant comorbid conditions. The study was planned as a retrospective, multicenter and cross-sectional study. Thirty-nine SCD patients, ages 18 to 64 years, and 121 healthcare professionals, ages 21 to 53, were included in the study. The data were collected from the Electronic Health Recording System of PRANA, where SCD patients under the BASCARE program had been registered. The data of other patients were collected from the Electronic Hospital Data Recording System and patient files. In the SCD group, the crude incidence of COVID-19 was 9%, while in healthcare professionals at the same period was 23%. Among the symptoms, besides fever, loss of smell and taste were more prominent in the SCD group than in healthcare professionals. There was a significant difference between the two groups in terms of development of pneumonia, hospitalization, and need for intubation (43 vs 5%, P < 0.00001; 26 vs 7%, P = 0.002; and 10 vs 1%, P = 0.002, respectively). Prophylactic low molecular weight heparin and salicylate were used more in the SCD group than in healthcare professionals group (41 vs 9% and 28 vs 1%; P < 0.0001 for both). The 3-month mortality rate was demonstrated as 5% in the SCD group, while 0 in the healthcare professionals group. One patient in the SCD group became continously dependent on respiratory support. The cause of death was acute chest syndrome in the first case, hepatic necrosis and multi-organ failure in the second case. In conclusion, these observations supported the expectation that the course of COVID-19 in SCD patients will get worse. The BASCARE program applied in SCD patients could not change the poor outcome.

Comparison of Outcomes of Transplant and Nontransplant High-Risk Chronic Lymphocytic Leukemia Patients in the Novel Targeted Therapy Era.

OBJECTIVES: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred to our transplant center who underwent allogeneic stem cell transplant with those who did not receive this treatment. Factors compared included demographics, clinical characteristics, and survival rates in the novel targeted therapy era. MATERIALS AND METHODS: All 33 patients with high-risk chronic lymphocytic leukemia who were referred to the hematopoietic stem cell transplant center were enrolled in this retrospective, single-center nonrandomized study. Outcomes of patients who received allogeneic stem cell transplant were compared with those of nontransplant patients. Chemoimmunotherapy and ibrutinib were given when indicated. Factors related to overall and progression-free survival were assessed. RESULTS: Thirteen patients underwent allotransplant, and transplant was not done in 20 patients for various reasons. Demographic and clinical features of the transplant and nontransplant groups were similar. The estimated cumulative overall survival was 72.6 ± 15 and 84.3 ± 13 months in the nontransplant and transplant groups, respectively. The 5-year overall and progression-free survival rates in the transplant and nontransplant groups were 57.3%/36.0% and 40%/20.6%, respectively. In the nontransplant group, overall survival of those who used ibrutinib was longer than overall survival in patients in the transplant group who used the same drug, but the difference was not statistically significant. Although not significant, overall survival in patients who did not use ibrutinib was longer in the transplant group than in the nontransplant group. Cox regression analyses showed that transplant, relapse, and Binet stage were independent predictors of overall survival. CONCLUSIONS: In patients who do not use ibrutinib, allogeneic stem cell transplant improved survival compared with nontransplant patients. Addition of ibrutinib provided comparable life expectancies, showing that allogeneic stem cell transplant and ibrutinib may have complementary roles. Transplant is still an independent predictor of overall survival.

Factors Associated With Overall Survival in Acute Myeloid Leukemia Patients Before and After Hematopoietic Stem Cell Transplant.

OBJECTIVES: Our aim was to identify factors associated with overall survival and the efficacy of postrelapse treatment protocols and to determine whether pretransplant consolidation therapy and minimal residual disease status pose a survival benefit. MATERIALS AND METHODS: Patients with acute myeloid leukemia who underwent stem cell transplant between 2007 and 2018 were enrolled retrospectively. The effects of pretransplant cytogenetic and minimal residual disease status, pretransplant consolidation therapies, development of graft-versus-host disease, postrelapse treatment protocols, and type of con-ditioning regimens on overall survival were analyzed. RESULTS: In 76 study patients, the cumulative overall 1- and 5-year relapse probabilities were 67.8% and 58.7%, respectively. Overall survival rates at 3 and 5 years in patients with and without relapse were 23.5% and 0% and 95.9% and 91.1% (P < .001), respectively. Although mean postrelapse overall survival was better with intensive salvage plus donor lymphocyte infusion, no significant differences were shown versus other therapies (intensive salvage, nonintensive salvage, intensive salvage or nonintensive salvage plus donor lymphocyte infusion, or supportive therapy). Twenty-three patients (30.3%) died during the study period with a median survival of 9.6 months. Patients with favorable, intermediate, and unfavorable cytogenetic status showed overall survival of 46.6 ± 10.4, 54.6 ± 4.4, and 36.9 ± 5.9 months (P = .807). Patients with and without minimal residual disease and patients who received or did not receive consolidation therapy had similar overall survival. Relapse was an independent predictor of overall survival (increased mortality risk of 26.22). Patients who developed graft-versus-host disease showed decreased relapse. CONCLUSIONS: Relapse is the most important predictor of overall survival and is associated with poor prognosis. Pretransplant minimal residual status and cytogenetic status showed no effect on relapse rates and overall survival, and consolidation therapy did not improve outcomes.

The Impact of the Ferric Carboxymaltose on Hemoglobin and Ferritin Levels.

BACKGROUND: Anemia is a frequent disorder worldwide. Iron deficiency anemia (IDA) is the most common form of anemia. Although oral iron is the first choice for treatment, the efficacy of oral iron preparations may be limited. Ferric carboxymaltose (FCM) is a novel parenteral iron preparation which can rapidly replenish iron stores. The aim of the present study is to investigate the impact of FCM dose on hemoglobin (Hb) and ferritin levels and the frequency of hypersensitivity reactions. METHODS: This study was conducted with 765 IDA patients between September 1, 2016 and September 1, 2018. He-moglobin (Hb), serum ferritin, transferrin saturation values were examined at the time of diagnosis, Hb and ferritin values at first month. RESULTS: Post-treatment Hb and ferritin levels significantly increased. The mean Hb level alteration was 2.43 ± 1.2 g/dL, the median ferritin level alteration was 157.3 ng/mL. The mean Hb level was lower and the mean change in Hb level was higher in higher doses. Allergic reactions were more frequent in higher doses. CONCLUSIONS: Ferric carboxymaltose is a novel treatment option with a low risk of hypersensitivity reactions and well tolerated even in high doses.

Frequency of Finding Family Donors: A Single Center Experience.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant is a curative treatment option for many hematologic diseases. The existence of a fully compatible donor for recipients is the first condition for minimized transplant-related mortality and morbidity. The best donor for hematopoietic stem cell transplant is an HLA-matched sibling donor. The possibility of finding an HLA-matched sibling is less than 30% worldwide. Hematopoietic stem cell transplant is needed for an increasing number of patients every year, but the ability to find a fully compatible donor has limited its use. MATERIALS AND METHODS: From August 2012 to May 2017, we screened 412 adult patients who required AHSCT and their families for HLA tissue groups who were seen at our center (Baskent University Adana Dr. Turgut Noyan Research and Medical Center Hematology Unit). To screen tissue groups at our center, we perform lowresolution typing for HLA-A, -B, -C, -DRB1, and -DQB. If an HLA genotype cannot be identified, verification typing is done using highresolution testing. RESULTS: We found matched family donors in 227 (55%) of 412 patients screened at our center. The ratio of HLAmatched related donors was 83% for 279 patients who received allogeneic stem cell transplant. CONCLUSIONS: The likelihood of finding eligible unrelated donors has been gradually increasing, in part due to the development of the National Bone Marrow Bank. However, a careful screening for related donors is still important. Our findings indicate the importance of careful examination of family genealogy and of careful family screening in our region.

Organ damage mitigation with the Baskent Sickle Cell Medical Care Development Program (BASCARE).

The Eastern Mediterranean is among the regions where sickle cell disease (SCD) is common. The morbidity and mortality of this disease can be postponed to adulthood through therapies implemented in childhood. The present study focuses on the organ damage-reducing effects of the Baskent Sickle Cell Medical Care Development Program (BASCARE), which was developed by a team who lives in this region and has approximately 25 years of experience. The deliverables of the program included the development of an electronic health recording system (PRANA) and electronic vaccination system; the use of low citrate infusion in routine prophylactic automatic erythrocyte exchange (ARCE) programs including pregnant women; the use of leukocyte-filtered and irradiated blood for transfusion; the use of magnetic resonance imaging methods (T2) for the management of transfusion-related hemosiderosis; and the implementation of an allogeneic hematopoietic stem cell transplantation protocol for adult patients. The sample was composed of 376 study subjects and 249 control subjects. The hospital's Data Management System and the central population operating system were used for data collection. BASCARE enabled better analysis and interpretation of complication and mortality data. Vaccination rates against influenza and pneumococcal disease improved (21.5% vs 50.8% and 21.5% vs 49.2%, respectively). Effective and safe ARCE with low citrate infusion were maintained in 352 subjects (1003 procedures). Maternal and fetal mortality was prevented in 35 consecutive pregnant patients with ARCE. Chelating therapy rates reduced from 6.7% to 5%. Successful outcomes could be obtained in all 13 adult patients who underwent allogeneic peripheral stem cell transplantation from a fully matched, related donor. No patients died by day 100 or after the first year. Cure could be achieved without graft loss, grades III to IV acute graft versus host disease, extensive chronic graft versus host disease, or other major complications. The BASCARE program significantly improved patient care and thereby prolonged the life span of SCD patients (42 ± 13 years vs 29 ±â€Š7 years, P < .001). We may recommend using such individualized programs in centers that provide health care for patients with SCD, in accordance with holistic approach due to the benign nature but malignant course of the disease.

Anti-HLA Antibody Levels Are Associated With the Risk of Graft Failure After Allogeneic Hematopoietic Stem Cell Transplant.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant provides a curative treatment for a considerable amount of hematologic diseases, and it is widely used today. Successful allogeneic stem cell transplant can be compromised by treatment-related toxicity, graft-versus-host disease, infectious complications, disease relapse, and graft failure. Primary graft failure is an important cause of hematopoietic stem cell transplant failure. Primary graft failure correlates with the level of complement-binding, donor-specific anti-HLA antibodies prior to transplant. MATERIALS AND METHODS: We evaluated 15 patients who underwent hematopoietic stem cell transplant using peripheral blood stem cells in terms of graft failure and anti-HLA antibody levels before transplant. All were treated between January 2015 and June 2016. Pretreatment serum anti-HLA class I and anti-HLA class II antibody levels were measured in all patients. RESULTS: Anti-HLA class I antibodies were present in 7 patients (46.6%) and anti-HLA class II antibodies in 8 (53.3%). All three patients who developed primary graft failure were anti-HLA-positive. CONCLUSIONS: Anti-HLA antibodies are a significant cause of graft failure. It is a situation that must be understood with caution. Our results support the considerations that allogeneic hematopoietic stem cell transplant, especially when a fully compatible sibling donor is not present, should include screening of donor-specific antibodies of alternative donors and desensitization therapy for allosensitized patients before transplant.

East Mediterranean region sickle cell disease mortality trial: retrospective multicenter cohort analysis of 735 patients.

Sickle cell disease (SCD), one of the most common genetic disorders worldwide, is characterized by hemolytic anemia and tissue damage from the rigid red blood cells. Although hydroxyurea and transfusion therapy are administered to treat the accompanying tissue injury, whether either one prolongs the lifespan of patients with SCD is unknown. SCD-related mortality data are available, but there are few studies on mortality-related factors based on evaluations of surviving patients. In addition, ethnic variability in patient registries has complicated detailed analyses. The aim of this study was to investigate mortality and mortality-related factors among an ethnically homogeneous population of patients with SCD. The 735 patients (102 children and 633 adults) included in this retrospective cohort study were of Eti-Turk origin and selected from 1367 patients seen at 5 regional hospitals. A central population management system was used to control for records of patient mortality. Data reliability was checked by a data supervision group. Mortality-related factors and predictors were identified in univariate and multivariate analyses using a Cox regression model with stepwise forward selection. The study group included patients with homozygous hemoglobin S (Hgb S) disease (67 %), Hb S-ß(0) thalassemia (17 %), Hgb S-ß(+) thalassemia (15 %), and Hb S-α thalassemia (1 %). They were followed for a median of 66 ± 44 (3-148) months. Overall mortality at 5 years was 6.1 %. Of the 45 patients who died, 44 (6 %) were adults and 1 (0.1 %) was a child. The mean age at death was 34.1 ± 10 (18-54) years for males, 40.1 ± 15 (17-64) years for females, and 36.6 ± 13 (17-64) years overall. Hydroxyurea was found to have a notable positive effect on mortality (p = 0.009). Mortality was also significantly related to hypertension and renal damage in a univariate analysis (p = 0.015 and p = 0.000, respectively). Acute chest syndrome, splenic sequestration, and prolonged painful-crisis-related multiorgan failure were the most common causes of mortality. In a multivariate analysis of laboratory values, only an elevated white blood cell count was related to mortality (p = 0.009). These data show that despite recent progress in the treatment of SCD, disease-related factors continue to result in mortality in young adult patients. Our results highlight the importance of evaluating curative treatment options for patients who have an appropriate stem cell donor in addition to improving patient care and patient education.

Anorectal Complications During Neutropenic Period in Patients with Hematologic Diseases.

BACKGROUND: Neutropenic patients are susceptible to any anorectal disease, and symptomatic anorectal disease afflicts 2-32% of oncology patients. Perianal infections are the most feared complication, considering the lack of natural defense against infectious microorganisms. When septic complications develop, the anorectal disease is potentially fatal, especially in neutropenic patients in whom mortality rates range between 11-57%. Although anorectal diseases are a frequent complication with potentially fatal outcomes among patients with hematologic diseases, sufficient data are not available in the literature. In this study, we aimed to investigate the anorectal complications developing during the neutropenic period in patients with hematologic diseases. METHODS: A total of 79 patients whose neutropenic period (absolute neutrophil count <500/mcL) continued for 7 days, or longer were included in the study. RESULTS: A total of 34 patients out of 79 (43%) were detected to develop anorectal complications, of them 6 (7.6%) developed an anorectal infection. The patients were characterized according to the hematological disease and its status (active or not), the type of treatment and the presence of a history of an anorectal pathology before the onset of the hematologic disease. Nineteen (24.1%) patients had the history of anorectal disturbances before diagnosis of the hematologic disease, and recurrence of an anorectal pathology was found in 14 out of 19 patients(73.7%). In addition, the overall mortality rate was higher among the patients who developed anorectal complications compared to another group (41.2% vs. 22.2%, p=0.059). CONCLUSION: Anorectal pathology is a common complication with high recurrence rate in neutropenic patients. Perianal infections are important as they can cause life-threatening outcomes although they are relatively rare among all anorectal complications. Therefore perianal signs and symptoms should be meticulously evaluated concerning early diagnosis and treatment.

Clinical Relevance of Apheretic Graft Composition in Patients With Acute Myeloblastic Leukemia Who Received a Busulfan-Fludarabine-Antithymocyte Globulin Conditioning Regimen for Allogeneic Transplant.

OBJECTIVES: Sparse data are available about the effects of apheretic graft composition on the clinical transplant outcome in allotransplanted patients who have hematologic malignant disease. Major obstacles in recent studies have included heterogeneity of patient populations and differences in the conditioning regimens used. MATERIALS AND METHODS: This prospective study included 50 patients who had acute myeloblastic leukemia and received busulfan-fludarabine-antithymocyte globulin-based conditioning for peripheral allogeneic stem cell transplant. The concentration of CD34+ cells, T-cell subsets, B cells, and natural killer cells in the graft were analyzed by flow cytometry in the donors who were matched for human leukocyte antigen. RESULTS: In univariate analysis, infusion with a higher dose of natural killer cells (> 1.55 × 106/kg) was associated with improved survival (P = .007 for disease-free survival; P = .024 for overall survival) in patients with acute myeloblastic leukemia. Cox regression models revealed that increased concentration of natural killer cells and CD34+ cells positively affected the clinical outcome of allotransplanted patients (P = .005 for both cell types). According to univariate analysis, these findings were dependent on minimal residual disease and acute graft-versus-host disease. Graft-versus-host disease (acute and chronic forms) was not affected by graft composition. CONCLUSIONS: Our results suggest that increased concentration of natural killer cells and CD34+ cells in the apheretic product may predict better survival. In contrast, busulfan-fludarabine-antithymocyte globulin-based conditioning eliminates the disadvantages that resulted from the high content of T-cell subsets and B cells, and the course of the transplant and clinical parameters were not affected by the amount of T and B cells.

Prophylactic red blood cell exchange may be beneficial in the management of sickle cell disease in pregnancy.

BACKGROUND: Sickle cell disease (SCD) is associated with chronic hemolysis and painful episodes. Pregnancy accelerates sickle cell complications, including prepartum and postpartum vasoocclusive crisis, pulmonary complications, and preeclampsia or eclampsia. Fetal complications include preterm birth and its associated risks, intrauterine growth restriction, and a high rate of perinatal mortality. The purpose of this study was to evaluate pregnancy outcomes in patients with SCD who underwent planned preventive red blood cell exchange (RBCX). STUDY DESIGN AND METHODS: We retrospectively evaluated the complications of SCD in 37 pregnant patients. Patients with SCD who had undergone prophylactic RBCX were compared with a control group who had not undergone RBCX during pregnancy. RESULTS: Forty-three exchange procedures were performed in 24 patients. The control group comprised 13 patients with a mean age of 27.4 ± 3.3 years who had not undergone RBCX during pregnancy. Four of the five patients who developed a vasoocclusive crisis died. There was a significant difference in maternal mortality between the study and control groups (p = 0.011). There was also a significant difference in the incidence of vasoocclusive crisis between the study and control groups. One fetal death occurred in the 20th gestational week in a patient in the control group, although there were no postpartum complications in either the babies or the mothers in the control group. CONCLUSION: This study has demonstrated that prophylactic RBCX during pregnancy is a feasible and safe procedure for prevention of complications. Given the decrease in the risks of transfusion, RBCX warrants further study.

Clinical significance of circulating blood and endothelial cell microparticles in sickle-cell disease.

Increased thrombocyte activation leads to a higher likelihood of coagulation in sickle-cell disease. On the other hand, chronic inflammation and endothelial cell activation promote vaso-occlusion. The effect of circulating microparticles derived from erythrocytes, monocytes, thrombocytes, and endothelial cells on the vaso-occlusive process is unclear. This study aims to analyze the relationship between sickle-cell disease and miscellaneous organ complications by defining the circulating microparticles during the steady-state and painful crisis periods in 45 patients with sickle-cell disease. Microparticle analysis was conducted using an eight-parameter flow cytometric method, using CD61 PERCP, CD142PE, CD106 FITC, CD14 APC-H7, CD235a FITC, and Annexin-V APC monoclonal antibodies. Microparticle levels of sickle-cell patients were found to be significantly higher during both painful crisis and steady-state situations compared with the control group (for all, p < 0.001). Among these microparticles, levels of erythrocyte microparticles (eMPs) were significantly higher during crisis than in the steady-state period (eMP steady state vs. painful crisis: 7.59 ± 12.24 vs. 7.59 ± 12.24, respectively; p < 0.01). Microparticles, including eMPs, were not affected by hydroxyurea treatment. Their level did not reflect the high frequency of crisis (>3 times/year). Thrombocyte microparticle levels were found to be higher in patients with nephropathia than in those without (48.05 ± 40.23 vs. 7.67 ± 6.75, respectively; p < 0.049). Circulating microparticles seem to be involved in the pathogenesis of sickle-cell disease. eMPs may help with the management of crisis. Thrombocyte microparticles might predict renal damage induced by vaso-occlusion.

Short-term central venous catheter complications in patients with sickle cell disease who undergo apheresis.

Patients with sickle cell disease (SCD) are prone to develop thrombosis and infection due to their inflammatory and immune deficiency state. These patients require red cell exchange therapy for treatment or prevention of hemoglobin S associated complications. Owing to vascular access problems, adult patients need central venous catheterization (CVC) for exchange procedures. Procedure related complications have been reported for long-term CVCs in pediatric patients. However, short-term CVC complications in adult patients are not clear. This report represents the results of documented complications of short-term CVCs in patients with SCD who undergo apheresis. A total of 142 non-tunneled catheters with average median diameter of 9 F (range 8-16 F) were implanted for apheresis. The catheters were mainly inserted through the right internal jugular vein (66.2 %). Total days of catheter were 412. Results were reported as a complication rate and event according to 1,000 catheter days and compared to a control group including 37 healthy stem cell donors. In the patient group, 1 (1 %) hematoma and 1 (1 %) infection were observed for internal jugular vein catheterization (3.7 hemorrhages and 3.7 infections according to 1,000 catheter days), whereas four (8.9 %) cases of thrombosis and 1 (2.2 %) infection (27 and 6.9 according to 1,000 catheter days) developed in femoral vein. There was a significant difference in terms of thrombosis (P = 0.009). In the control group, only individual developed thrombosis in internal jugular vein. Short-term CVC inserted through to the internal jugular vein seems to be safer than femoral vein in patients with SCD.

Cranial involvement in sickle cell disease.

PURPOSE: To evaluate cranial findings in patients with neurologically symptomatic sickle cell disease (SCD). MATERIALS AND METHODS: We studied 50 consecutive patients with SCD and neurologic symptoms. All patients underwent brain MR examinations: all 50 underwent classic MR imaging; 42, diffusion-weighted MR imaging; 10, MR angiography; four, MR venography; and three patients, digital subtraction angiography. RESULTS: Of the 50 SCD patients, 19 (38%) had normal MR findings, and 31 (62%) showed abnormalities on brain MR images. Of the 50 patients, 16 (32%) had ischemic lesions; two (4%), subarachnoid hemorrhage; one (2%), moya-moya pattern; one (2%), posterior reversible encephalopathy; one (2%), dural venous sinus thrombosis; 12 (24%), low marrow signal intensity and thickness of the diploic space; 12 (24%), cerebral atrophy; and two (4%), osteomyelitis. Twenty-seven patients (54%) presented with headache, which was the most common clinical finding. CONCLUSIONS: The cranial involvement is one of the most devastating complications of SCD. Early and accurate diagnosis is important in the management of cranial complications of SCD.