Haematopoietic cytopenia associated with cyclin-dependent kinase 4/6 inhibitors: A real-world study of data from the food and drug administration adverse event reporting system database.

OBJECTIVE: The haematopoietic cytopenia (HC) of the cyclin-dependent kinase (CDK)4/6 inhibitors was evaluated using the Food and Drug Administration Adverse Event Reporting System (FAERS). METHOD: Data from 1 January 2015 to 31 December 2021 has been retrieved from the FAERS database. Disproportionality analysis and Bayesian analysis were utilized in the data mining. The reporting odds ratio (ROR) with 95% confidence interval (CI) for HC was calculated for each CDK 4/6 inhibitor agent. Clinical features of the patients were collected and compared between death outcome and non-death outcome groups. Time to onset (TTO), proportion of deaths, life-threatening and hospitalizations of CDK 4/6 inhibitors-associated HC were also studied. RESULTS: A total of 17,235 cases of HC associated with CDK 4/6 inhibitors were identified with a median age of 65 years (interquartile range [IQR] 57-73). Palbociclib appeared the strongest signal, with the highest (ROR 9.64, 95% CI 9.46-9.83), followed by ribociclib (ROR 6.38, 95% CI 6.04-6.73) and then abemaciclib (ROR 2.72, 95% CI 2.49-2.97). Patients aged 18-64 had a higher proportion of deaths than those aged 65-84 (12.21% vs. 9.91%, p = 0.001). In Africa and Asia, the proportions of deaths were higher (31.65% and 26.13%, respectively). The median TTO was 26 days (IQR 14-65) for abemaciclib, 33 days (IQR 15-134) for palbociclib and 23 days (IQR 14-69) for ribociclib, respectively. The highest proportion of deaths, life-threatening and hospitalizations all occurred in abemaciclib (13.00%, 5.42% and 44.04%, respectively). CONCLUSIONS: Greater proportions of deaths occurred in Africa and Asia. HC may occur early in any CDK 4/6 inhibitor regimen. Abemaciclib had the highest proportion of deaths, life-threatening and hospitalizations. Health care workers should be more concerned about CDK 4/6 inhibitors. The higher proportions of serious events, including deaths, from Africa and Asia, as well as for abemaciclib, deserve further investigations through additional pharmacoepidemiological approaches.

Gold-Nanohybrid Biosensors for Analyzing Blood Circulating Clinical Biomacromolecules: Current Trend toward Future Remote Digital Monitoring.

Mortality level is worsening the situation worldwide thru blood diseases and greatly jeopardizes the human health with poor diagnostics. Due to the lack of successful generation of early diagnosis, the survival rate is currently lower. To overcome the present hurdle, new diagnostic methods have been choreographed for blood disease biomarkers analyses with the conjunction of ultra-small ideal gold nanohybrids. Gold-hybrids hold varieties of unique features, such as high biocompatibility, increased surface-to-volume ratio, less-toxicity, ease in electron transfer and have a greater localized surface plasmon resonance. Gold-nanocomposites can be physically hybrid on the sensor surface and functionalize with the biomolecules using appropriate chemical conjugations. Revolutionizing biosensor platform can be prominently linked for the nanocomposite applications in the current research on medical diagnosis. This review encloses the new developments in diagnosing blood biomarkers by utilizing the gold-nanohybrids. Further, the current state-of-the-art and the future envision with digital monitoring for facile telediagnosis were narrated.

Practical management of patients with hematological diseases during the COVID-19 pandemic in Japan.

Polymerase chain reaction (PCR) tests cannot always detect the SARS-CoV-2 virus, possibly due to differences in sensitivity between sample types. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that indicate a history of infection. In our analysis of patients with severe COVID-19 infection, we found that 14 of 19 serum samples were positive for IgG antibodies, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative. Two patients with immune thrombocytopenia who were treated with prednisolone experienced aggressive COVID-19-related respiratory failure and eventually died. Patients not in remission and those who received steroid-based chemotherapy had a higher risk of death, and patients with lymphoid malignancies including lymphoma and myeloma died in larger numbers than those with myeloid malignancies. A stricter cohorting strategy based on repeat PCR tests or isolation to a private room should be adopted in routine care in hematology departments to prevent viral spread to the environment.

Clinical characteristics and risk factors associated with nosocomial COVID-19 infection in patients with hematological disorders in Japan.

Patients with cancer are considered at high risk of acquiring coronavirus disease (COVID-19). To identify patients who are likely to be diagnosed with severe COVID-19, we analyzed the risk factors for mortality in patients admitted to the hematology department at our institute. The mortality rate of all patients was as high as 62% (21 of the 34 patients), and most of these patients had malignant malignancies. Patients before an achievement of remission had a 10.8-fold higher risk of death than those in remission. The group receiving chemotherapy with steroids had a shorter survival time and had an 8.3-fold higher risk of death than that receiving chemotherapy without steroids. During the COVID-19 pandemic, it is necessary to carefully monitor or follow-up patients with active diseases and patients receiving steroid-containing chemotherapy.

Interplay Between the Intestinal Microbiota and Acute Graft-Versus-Host Disease: Experimental Evidence and Clinical Significance.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many hematological disorders and autoimmune diseases, but acute graft-versus-host disease (aGVHD) has remained a major obstacle that limits allo-HSCT and exhibits a daunting mortality rate. The gastrointestinal system is among the most common sites affected by aGVHD. Experimental advances in the field of intestinal microbiota research enhanced our understanding - not only of the quantity and diversity of intestinal microbiota - but also their association with homeostasis of the immune system and disease pathogenesis, including that of aGVHD. Meanwhile, ever-growing clinical evidence suggest that the intestinal microbiota is dysregulated in patients who develop aGVHD and that the imbalance may affect clinical outcomes, indicating a potential predictive role for microbiota dysregulation in aGVHD severity and prognosis. The current animal and human studies investigating the intestinal microbiota in aGVHD and the understanding of the influence and management of the microbiota in the clinic are reviewed herein. Taken together, monitoring and remodeling the intestinal microecology following allo-HSCT may provide us with promising avenues for diagnosing, preventing or treating aGVHD in the clinic.

Ethnic and border differences on blood cancer presentation and outcomes: A Texas population-based study.

BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

The clinical implications of clonal hematopoiesis in hematopoietic cell transplantation.

Clonal hematopoiesis (CH) describes somatic mutations in hematopoietic stem and progenitor cells resulting in clonal expansion in individuals with no overt hematologic disease. Since CH increases in an age-related manner, understanding its role in hematopoietic cell transplantation (HCT) has become increasingly relevant to an aging transplant population. Multiple factors distinguish post-transplant hematopoiesis from unperturbed, steady-state hematopoiesis, including the influence of immunosuppressants, cytotoxic reagents, and marked proliferative stress, all of which may enhance or diminish the opportunity for clonal expansion. We reviewed the available clinical evidence on the consequences of CH at time of transplant in patients undergoing autologous HCT, and the impact of donor and recipient CH on allogeneic HCT outcomes. In the absence of evidence-based guidelines, we share our suggestions for managing donors and recipients found to have CH. Large-scale studies are needed to guide an evidence-based, uniform approach for the management of CH in the setting of HCT.

Long-term Outcomes of Sequential Hematopoietic Stem Cell Transplantation and Kidney Transplantation: Single-center Experience.

BACKGROUND: Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited. METHODS: We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y. RESULTS: In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group. CONCLUSIONS: Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.

Comparison of Risk Scoring Systems in HLA-Matched Related Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

Objective: Allogeneic hematopoietic stem cell transplantation (AHSCT) is a potentially curative treatment of choice for many hematological diseases. However, there are some transplantation-related risks. Predicting the risk-benefit ratio prior to AHSCT facilitates the choice of conditioning regimens and posttransplant follow-up. Hence, many risk models have been developed. The aim of the present study was to compare 6 different risk models that are clinically used. Materials and Methods: A total of 259 patients were enrolled in this study. The European Society for Blood and Marrow Transplantation (EBMT), Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), Age-Adjusted Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI-Age), revised Pretransplant Assessment of Mortality (rPAM), Acute Leukemia-EBMT (AL-EBMT), and Disease Risk Index (DRI) risk models were applied retrospectively. Results: The AL-EBMT, HCT-CI, and HCT-CI-Age scoring systems were found to be predictive for 2-year overall survival (OS) and 2-year non-relapse mortality (NRM) (2-year OS: AL-EBMT, reference vs. score 8.5-10, HR: 1.3, p=0.035; AL-EBMT, reference vs. score >10, HR: 3.8, p=0.001; HCT-CI: reference vs. score 1-2, HR: 1.4, p=0.018; HCT-CI: reference vs. score ≥3, HR: 2.5, p<0.001; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p<0.001; HCT-CI-Age: reference vs. score ≥3, HR: 3.2, p<0.001) (2-year NRM: AL-EBMT: reference vs. score 8.5-10, HR: 1.61, p<0.001; AL-EBMT: reference vs. score >10, HR: 3.3, p<0.001; HCT-CI: reference vs. score 1-2, HR: 1.3, p=0.028; HCT-CI: reference vs. score ≥3, HR: 2.3, p=0.011; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p=0.01; HCT-CI-Age: reference vs. score ≥3, HR: 2.4, p=0.003). In terms of the Kaplan-Meier estimates of 2-year OS and 2-year NRM, the risk scoring system with the highest predictive power was found to be AL-EBMT (2-year AUC: 0.59 and 0.60, respectively). The other scores were not found to be predictive for 2-year OS and NRM. Conclusion: In the present study at our bone marrow and stem cell transplant center, it has been demonstrated that the HCT-CI, HCT-CI-Age, and AL-EBMT are good predictors of 2-year NRM and OS.

The Expression of MicroRNA-21 in Bone Marrow Fluid is an Indicator of Hematological Disorders and Mortality.

OBJECTIVE: Bone marrow fluid (BMF) consists of various components that establishes a microenvironment for cell differentiation and remodeling. MicroRNA-21 (miR-21) levels have recently emerged as novel biomarkers for different diseases. However, the conventional RNU6B (U6), used as the reference for intracellular miRNA, may not be appropriate for the normalization of circulating miRNAs. METHODS: We measured the levels of U6, spiked-in RNA, and miR-21 in the BMF of 13 healthy controls and 37 patients with hematological disorders to investigate the reliability of either U6 or spike-in RNA as an endogenous reference and also to study the correlation between miR-21, hematological disorders and mortality. RESULTS: Notably, the levels of U6 demonstrated a high variability in BMF of healthy controls and patients. In contrast, the levels of spiked-in RNA displayed a significantly higher stability in both cohorts. Compared with controls, the levels of miR-21 were significantly upregulated in BMF of patients with leukemia but not lymphoma. Also, using 21 as the cut-off value of miR-21, it differentiated the mortality of patients with hematologic disorders. CONCLUSIONS: Collectively, using spiked-in RNA as a reference the upregulated miR-21 levels in BMF could be an indicator of the diagnosis of leukemia and a predictor of mortality.

Clinical outcomes and risk factors for severe COVID-19 in patients with haematological disorders receiving chemo- or immunotherapy.

Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.

Adenovirus Viral Kinetics and Mortality in Ex Vivo T Cell-Depleted Hematopoietic Cell Transplant Recipients With Adenovirus Infection From a Single Center.

BACKGROUND: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). METHODS: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. RESULTS: Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180. CONCLUSIONS: In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.

[The impact of carbapenem-resistance Pseudomonas aeruginosa infections on mortality of patients with hematological disorders].

Objective: To assess the risk factors for mortality and clinical outcome of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections in patients with hematological disorders. Methods: The data of in-patients with hematological disorders infected by CRPA or carbapenem-susceptible Pseudomonas aeruginosa (CSPA) were recorded in a seven-year retrospective cohort study. Risk factors for CRPA infections and impact of on mortality were identified. The primary end point was 30-day all-cause mortality. Results: A total of 81 patients with PA infections were included in the study, including 58 CSPA and 23 CRPA. Most of the primary diseases were acute leukemia or lymphoma (79.0%, 64/81). The median absolute neutrophil count at infection onset was 0.24×10(9)/L. Independent risk factors associated with carbapenem-resistance included longer duration of hospital stay (P=0.013, OR=1.045) and carbapenem exposure one month prior to infections (P=0.005, OR=8.132). The 30-day all-cause mortality of the whole cohort was 29.6%(24/81), and 30-day attributable mortality was 13.6%(11/81). Pulmonary infection was the leading cause of death, accounting for 41.7%(10/24). The adjusted 30-day mortality rate was significantly higher in patients with CRPA compared with CSPA [60.9%(14/23) vs. 17.2%(10/58), P<0.001, respectively]. CRPA infection was an independent prognostic factor for 30-day mortality(P=0.011, OR=5.427). Other factors included old age, longer duration of neutropenia and poor functional performance. Conclusions: Patients with hematological disorders have high mortality rate and poor prognosis caused by CRPA infections, which mainly develop in lungs.

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases.

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability, and resistance to nuclease degradation. Aptamers and SOMAmers are largely employed for multiplex high-throughput proteomics analysis with high reproducibility and reliability, for tumor cell detection by flow cytometry or microscopy for research and clinical purposes. In addition, aptamers are increasingly used for novel drug delivery systems specifically targeting tumor cells, and as new anticancer molecules. In this review, we summarize current preclinical and clinical applications of aptamers in malignant and non-malignant hematological diseases.

IMPACT OF HLA-DPB1 MATCHING ON CLINICAL OUTCOMES AFTER HAPLOIDENTICAL-RELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION.

BACKGROUND: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. OBJECTIVE: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. METHODS: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. RESULTS: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. CONCLUSION: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Conditional Survival, Cause-Specific Mortality, and Risk Factors of Late Mortality After Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors' mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantified. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-specific mortality. METHODS: We calculated conditional survival rates and standardized mortality ratio for overall and cause-specific mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976-2014. Statistical tests were two-sided. RESULTS: The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15 years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% confidence interval [CI] = 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95% CI = 3.0 to 4.1). Primary disease accounted for 50% of deaths in the overall cohort and only 10% in 15-year survivors; the leading causes of nondisease-related mortality were subsequent malignancy (26.1%) and cardiopulmonary diseases (20.2%). We also identified the risk factors for nondisease-related mortality in 1- and 5-year survivors. CONCLUSION: Survival probability improves the longer patients survive after HCT. However, HCT recipients surviving 15 years or more remain at elevated mortality risk, largely because of health conditions other than their primary disease. Our study findings help inform preventive and interventional strategies to improve long-term outcomes after allogeneic HCT.

Two decades of experience in a combined adult/pediatric allogeneic hematopoietic stem cell transplantation center in Algiers, Algeria.

Hematopoietic stem cell transplantation (HSCT) has evolved from an experimental to a successful treatment modality reaching worldwide 80.000 HSCT/year. Distribution and trends of HSCT, however, remain heterogeneous. Activities range from none to more than 511/10 million population between countries and regions. Here, we report on a successful autologous and allogeneic HSCT program for adult and pediatric patients started two decades ago in Northern Africa. From 1998 to December 2017, a total of 2828 HSCT was performed of which 2059 were allo-HSCT (1474 adults and 585 children). The activities were analyzed according to indication, donor type, stem cell source, and trends over time. There was a significant difference in indications according to age. Adult patients were transplanted more often for hematological malignancies. In children, the indications were distributed equally between malignant and non-malignant diseases. Overall activities increased substantially in AML and to a lower extent in ALL and CLL despite sharp reduction of activity in CML after 2005. Finally, a higher transplantation rate (33/10 million population) was reached as compared to most regions of the world except Europe and USA/Canada. Overall survival in children with AML was 56.0% at 15 years, in adults 61.3% at 5 years, and in patients with CML 55.5% at 15 years without difference between reduced intensity condition (RIC) and myeloablative conditioning (MAC). Patients with Ph+ ALL had the lowest survival reaching 26.7% at 5 years. Highest survival was observed in patients with aplastic anemia, Fanconi anemia, and thalassemia reaching 77.3%, 73.5%, and 75.7% at 15 years respectively. Long distances and late referral remain a challenge for this large country.

The clinical impact of Stenotrophomonas maltophilia bacteremia on the 30-day mortality rate in patients with hematologic disorders: a single-institution experience.

OBJECTIVE: Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen, particularly in immunocompromised patients due to their adverse antimicrobial susceptibility pattern. The objective of this article was to investigate the clinical impact of SM bacteremia on the 30-day mortality rate and identify the risk factors of the cause of mortality in patients with hematologic disorders. METHODS: We retrospectively reviewed the clinical data in patients diagnosed with hematological disorders and SM bacteremia over an 8-year period from July 2010 to July 2018 at a 248-bed hematology department. We compared patients' clinical characteristics and outcomes between the non-survivor and survivor groups. RESULTS: The overall incidence of SM bacteremia was 25.1 per 10,000 admissions. There were 59 patients (median age: 35 years; 57.6% males) included in the study with an overall SM bacteremia-related 30-day mortality of 44.1%. Multi-drug resistance was common. In vitro susceptibility is higher to ceftazidime (72.9%), ciprofloxacin (66.1%) and cefoperazone/sulbactam (59.3%). The risk factors identified in the univariate analysis were catheter re-implantation, accompanying polymicrobial infection, inadequate initial antimicrobial treatment, APACHE II score, temperature > 39 °C, septic shock, respiratory failure, and non-remission post treatment for primary diseases. Multivariate analysis further confirmed that inadequate initial antimicrobial treatment, respiratory failure, and non-remission after treatment for hematological diseases are independent risk factors associated with mortality (P = 0.001, 0.002 and 0.007, respectively). CONCLUSIONS: Our study suggests that SM bacteremia is highly associated with increased mortality in patients with hematologic diseases. Early detection, prompt comprehensive management including initiation of combined sensitive antibiotics, respiratory monitoring and support, platelet infusion, and strategies to improve patients' remission status are recommended to improve the overall survival in patients with SM bacteremia.