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In more than 400 older patients with AML who could not receive myeloablative therapy, the incidence of composite complete remission was higher (66.4% vs. 28.3) and the median overall survival was longer (14.7 vs. 9.6 months) among patients who received azacitidine plus venetoclax (a B-cell lymphoma 2 antagonist) than among those who received azacitidine alone.

The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype ( P =3.82 × 10 −16 , odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm −3 ), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort ( P =1.92 × 10 −16 , odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype ( P =1.45 × 10 −4 ); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg −1 per day vs 1.03±0.425 mg kg −1 per day, P =6.21 × 10 −4 ). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with the T/T genotype. Low-dose 6MP (0.2–0.3 mg kg −1 per day) could be used rather than AZA for the patients with C/T genotype to continue thiopurine treatments. However, late leukopenia and other several adverse events could not be completely predicted by R139C genotypes.

Kyuyoung Song and colleagues report the results of a two-stage association study of thiopurine-induced early leukopenia in individuals undergoing treatment for Crohn's disease. They find a missense variant in NUDT15 associated with substantially higher risk of developing this life-threatening complication to thiopurine therapy. Thiopurine therapy, commonly used in autoimmune conditions, can be complicated by life-threatening leukopenia. This leukopenia is associated with genetic variation in TPMT (encoding thiopurine S-methyltransferase). Despite a lower frequency of TPMT mutations in Asians, the incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent. Here we performed an Immunochip-based 2-stage association study in 978 Korean subjects with Crohn's disease treated with thiopurines. We identified a nonsynonymous SNP in NUDT15 (encoding p.Arg139Cys) that was strongly associated with thiopurine-induced early leukopenia (odds ratio (OR) = 35.6; P combined = 4.88 × 10 −94 ). In Koreans, this variant demonstrated sensitivity and specificity of 89.4% and 93.2%, respectively, for thiopurine-induced early leukopenia (in comparison to 12.1% and 97.6% for TPMT variants). Although rare, this SNP was also strongly associated with thiopurine-induced leukopenia in subjects with inflammatory bowel disease of European descent (OR = 9.50; P = 4.64 × 10 −4 ). Thus, NUDT15 is a pharmacogenetic determinant for thiopurine-induced leukopenia in diverse populations.

The incidence of leukopenia and neutropenia associated with cytomegalovirus (CMV) prophylaxis in kidney transplant (KT) recipients is not well established. LECOCYT, a prospective observational multicenter study, aimed to investigate the clinical and economic burdens of CMV prophylaxis during the first 6 months post-transplantation. Grade 3 or 4 leukopenia or neutropenia was assessed in CMV-seropositive donors/CMV-seronegative recipients (D+/R-) who received current anti-CMV prophylaxis, and in CMV-seronegative donors/CMV-seronegative recipients (D-/R-) who did not. The economic burden in D+/R- was also evaluated. The adjusted odds ratio for grade 3 or 4 leukopenia or neutropenia was 5.16 [95% confidence interval: 1.97–13.53] for D+/R- group. The median costs, excluding the KT procedure, for D+/R- subgroup patients who experienced at least one episode of severe leukopenia or neutropenia were approximately €4,500 (Q1 = €561; Q3 = €10,000). D+/R- patients with no episode incurred significantly lower costs, with a median of nearly €2,100 (Q1 = €182; Q3 = €6,500) (p = 0.02). D+/R- patients with severe leukopenia or neutropenia had a higher rate of outpatient consultations than those without episode (73.9% vs. 57.6%, p = 0.002), and a higher average number of consultations per patient (5.5 ± 4.1 vs. 4.5 ± 3.3, p = 0.042) than D+/R- patients without. Anti-CMV prophylaxis in D+/R- transplant recipients was significantly associated with a higher rate of severe leukopenia or neutropenia compared to no prophylaxis in D-/R- recipients.

Background Acute appendicitis is a common surgical emergency, but its diagnosis can be challenging in patients with hematologic malignancies or chemotherapy-induced leukopenia due to an impaired inflammatory response. The clinical presentation of acute appendicitis in these patients is often atypical, leading to delayed or misdiagnosis. This study aims to evaluate the outcomes of appendectomy in patients with hematologic malignancies or chemotherapy-induced leukopenia and assess the applicability of clinical scoring systems for the diagnosis of an acute appendicitis. Methods We conducted a retrospective analysis of patients with hematologic malignancies or chemotherapy-related leukopenia who underwent appendectomy for suspected acute appendicitis between 2007 and 2023. Clinical presentation, laboratory findings, and imaging results were reviewed. The accuracy and relevance of clinical scoring systems for diagnosing acute appendicitis in these patients were also evaluated. Results Our study included 12 patients with hematologic malignancies or chemotherapy-induced leukopenia who underwent appendectomy. Atypical clinical presentations were common, with a lower frequency of fever, elevated leukocytes, and other typical inflammatory markers. Only one patient developed postoperative complications (acute kidney failure), and none of the patients died due to appendicitis. Clinical scoring systems demonstrated limited applicability in this patient population, often underestimating the likelihood of appendicitis. Conclusion Diagnosing acute appendicitis in patients with hematologic malignancies or chemotherapy-induced leukopenia poses significant challenges, as standard scoring systems prove unreliable. The presence of abdominal pain coupled with elevated C-reactive protein (CRP) levels should prompt a multidisciplinary evaluation and timely imaging. Surgical therapies, particularly laparoscopic approaches, appear safe and feasible in these patients. Ongoing research is essential to refine surgical strategies for the growing population of immunocompromised individuals.

Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland–Altman and Passing–Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 10 9 /L) and moderate and severe leukopenia (WBC < 1.5 × 10 9 /L) groups. For blast cells, immature granulocytes, and atypical lymphocytes, the DI-60 verification results were similar to the manual counting results. Plasma cells showed poor agreement. In conclusion, DI-60 demonstrates consistent and reliable analysis of WBC differentials within the range of 1.5–30.0 × 10 9 . Manual counting was indispensable in examining moderate and severe leucocytosis samples, moderate and severe leukopenia samples, and in enumerating of monocytes and plasma cells.

Background Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. Methods We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. Results Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn’s disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P  = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). Conclusion NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.

Hematological analysis has limited applications for disease diagnosis in Leishmania infantum-infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL) pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum-infected dogs: asymptomatic I (AD-I: serum negative/PCR+), asymptomatic II (AD-II: serum positive), oligosymptomatic (OD), and symptomatic (SD). Results were compared with those from noninfected dogs (NID). The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia), that contribute to CVL prognosis.

Thrombocytopenia and leucopenia are frequently encountered hematological disorders among people living with HIV/AIDS. This systematic review and meta-analysis were aimed to indicate the national prevalence of thrombocytopenia and leucopenia among HIV/AIDS patients. This systematic review and meta-analysis was conducted following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. A systematic search was conducted from February 01, 2021 to April 02, 2021 using electronic databases Google Scholar, PubMed, Web of Sciences, Google, EMBASE, SCOPUS and ResearchGate. The quality of the included studies was assessed using Newcastle-Ottawa Quality Assessment Scale (NOS) adapted for cross-sectional studies. Data analysis was done using STATA version 14 using metan commands. Random effect meta-analysis was used to estimate the pooled prevalence of thrombocytopenia and leucopenia among people living with HIV/AIDS in Ethiopia. Of the 349 initially searched articles, 90 were assessed for eligibility and only 13 articles published from 2014 to 2020 were included in the final meta-analysis. A total of 3854 participants were involved in the included studies. The pooled prevalence of thrombocytopenia was 9.69% (95%CI; 7.40-11.97%). Significant heterogeneity was observed with I2 value of 84.7%. Thrombocytopenia was 11.91% and 5.95% prevalent among HAART naive and HAART exposed HIV/AIDS patients, respectively. The pooled prevalence of leucopenia among HIV/AIDS patients was 17.31% (95%CI: 12.37-22.25%). This study showed a high prevalence of thrombocytopenia and leucopenia among people living with HIV/AIDS, indicating the necessity of regular screening of HIV seropositive patients for different hematological parameters and providing treatment.