Indian Journal of Hematology and Blood Transfusion最新文献

Anemia during pregnancy is one of the most common conditions that may have adverse consequences on maternal and fetal health. Current evidence is inconsistent with regards to the effects of anemia on maternal ICU admissions. This meta-analysis aimed to examine the overall effect of anemia during pregnancy on maternal ICU admissions. We searched PubMed, Embase, Cochrane Library, and Web of Science for observational studies that compared the risk of ICU admission between anemic and non-anemic pregnant women. We pooled the odds ratios (ORs) for ICU admission using a random-effects model. Heterogeneity among studies was assessed using prediction intervals (PIs), Tau² and I² statistics. Sensitivity analysis by excluding outlier studies, meta-regression by sample size and age, and publication bias detection by LFK index and Doi plot was undertaken. Eight studies with a total of 21,997,574 participants in both anemic and non-anemic groups were included. Of them, meta-analysis was conducted in seven studies which yielded a pooled OR for anemia and ICU admission as 1.32 (95% CI 0.62–2.81). There was also a very high level of heterogeneity among studies (PI: 0.10–18.16, I² = 100%). When an influential study was omitted, the pooled OR 1.16 (95% CI − 1.13; 1.20) for ICU admission was significant. The LFK index was − 3.64, indicating publication bias. Anemia in pregnant women might be associated with a higher risk of ICU admission, but it is essential to interpret this cautiously due to significant heterogeneity and potential publication bias.

Registration: PROSPERO database (CRD42023466529).

Cancer related microangiopathic hemolytic anemia is a rare entity and shares clinical and hematological features with other causes of thrombotic microangiopathy and leads to diagnostic dilemma and treatment delays. This record-based descriptive study, spanning five years, details the clinicopathological features with special emphasis on the peripheral blood findings in unsuspected cases of bone marrow metastasis of unknown primary in young adults. Seven relatively young patients, with an average age of 27 years, presented with unexplained anemia with peripheral blood showing features of microangiopathic hemolytic anemia, thrombocytopenia, and leukoerythroblastic picture. Subsequent bone marrow examination revealed presence of metastatic adenocarcinoma with the primary site being detected in five of the seven patients. This case series highlights these uncommon, but significant, hematological manifestations of metastatic adenocarcinoma in bone marrow in young adults, and the importance of astute observations of peripheral blood smear in detection of an underlying malignancy.

The transfusion-dependent form of thalassemia (TDT) presents as a challenging clinical scenario, requiring life-long care and monitoring. Managing a single TDT child is already very challenging for caregivers, and it becomes extremely burdensome if a couple has two children with TDT. The present study aims to make an effort to do a gap analysis in knowledge or communication, which might have resulted in a couple having two children with TDT. A total of 15 couples were identified who had two TDT children during the period from April 2022 to August 2023. Socio-demographic details, clinical history, three-generation pedigree, caregiver's knowledge about the inheritance pattern of thalassemia, the carrier status of 1st and 2nd-degree relatives, and the role of premarital and prenatal screening were recorded. The mean age difference between the first and second child was 2.6 ± 1.6 years, range 1–6 years. Siblings of 80% of TDT children had not been screened, and second-degree relatives of 86.6% of TDT children had not been screened for thalassemia. There was no history of consanguinity among these 15 families. 13.3% of couples were unaware of the inheritance pattern of thalassemia, and 20% were unaware of the role of consanguinity. At the time of interview, 26.6% of couples had not been tested for thalassemia and 40% parents had not received genetic counselling. Eighty percent of couples were unaware of premarital carrier screening for thalassemia, and only 40% knew about prenatal screening. The study highlights inadequate awareness among parents, delayed diagnosis, short intervals between the births of two children, insufficient genetic counselling, traditional societal beliefs, and reliance on traditional healing practices being the main factors leading to parents having two children with TDT.

This study investigates the efficacy and safety of generic plerixafor (Pleksor – Gen Pharma) compared to the original plerixafor (Mozobil - Sanofi) in patients with multiple myeloma undergoing ASCT. A total of 59 patients from three centers, who underwent ASCT between 2018 and 2023, were included and divided into two groups: Mozobil (M) group (n = 32) and Pleksor (P) group (n = 27). Plerixafor was administered as a just-in-time approach with granulocyte-colony stimulating factor (G-CSF) alone or with cyclophosphamide (Cy) + G-CSF mobilization. The study aimed to assess mobilization success and engraftment kinetics. There was no statistically significant difference between the two groups in terms of age, gender, RT history, previous lines of treatment, pretransplant lenalidomide cycles (p = 0.778, 0.165, 0.520, 0.094, 0.530, respectively). However, lenalidomide exposure was significantly higher in P group (18,8% vs. 81,5%, p < 0.001). Both groups achieved a similar total yield of CD34 + cells, and no serious side effects related to plerixafor were noted. Median platelet engraftment time was longer in P group, while neutrophil engraftment time was similar in both groups. This study demonstrates the comparable efficacy of generic plerixafor in myeloma patients, suggesting that it can be a cost-effective alternative with a similar safety profile. These findings contribute to the body of evidence on the use of generic plerixafor in specific patient cohorts, emphasizing its efficacy and safety for ASCT in a sole multiple myeloma patient cohort.

The impact of T-regulatory cells (Tregs), PD-1 + CD8 T-cells, and their dynamics during treatment with imatinib mesylate remains poorly understood in patients with chronic myeloid leukemia (CML). We conducted a prospective study on newly diagnosed, treatment-naïve adult (> 18 years old) patients with CML in the chronic phase (CP) and age- and sex-matched controls. Peripheral blood samples were collected at diagnosis and after three months of imatinib therapy to assess Tregs and PD-1 + CD8 T-cell levels using flow cytometry. The study comprised 57 patients with a median age of 39 years, including 27 males (47%). At baseline, the mean percentage of Tregs was significantly higher in CML patients (3.6 ± 0.32%) compared to controls (1.58 ± 0.21%) (p < 0.0001) but decreased significantly after three months of imatinib treatment (1.73 ± 0.35%) (p < 0.0001). Baseline Treg% exhibited positive correlations with Sokal (r = 0.29), Hasford (r = 0.33), EUTOS (r = 0.28), and ELTS (r = 0.31) risk scores (p < 0.05), as well as with the BCR-ABL transcript levels at three months (p = 0.03). Furthermore, the mean baseline percentage of PD-1 + CD8 T-cells was significantly elevated in CML patients (7.66 ± 0.36%) compared to controls (2.65 ± 0.32%) (p < 0.0001) and also decreased after treatment (3.44 ± 0.37%) (p < 0.0001). The baseline percentage of PD-1 + T-cells demonstrated positive correlations with Sokal (r = 0.26), Hasford (r = 0.27), and ELTS (r = 0.41) risk scores (p < 0.05). Our findings reveal a significantly higher proportion of Tregs and PD-1 + CD8 T-cells in patients with CML-CP compared to healthy controls, notably diminished following imatinib treatment. These observations suggest the potential for immunotherapy as a promising approach to managing immune exhaustion in CML patients.

Background

Systemic inflammatory response in diffuse large B-cell lymphoma (DLBCL) is closely related to disease prognosis. Our aim is to determine the role of pretreatment platelet-to-lymphocyte ratio (PLR) in predicting early treatment response in DLBCL patients.

Methods

This retrospective study included 94 patients. The correlation of PLR at the time of diagnosis with early treatment response was evaluated.

Results

66 patients responded to treatment and 28 patients were unresponsive or partially responsive. In univariate analysis, age, eastern cooperative oncology group performance status (ECOG-PS), disease stage, extranodal involvement, neutrophil-to-lymphocyte ratio (NLR), PLR, hemoglobin, albumin, lymphocyte, platelet (HALP) score were found to predict response to treatment. Multivariate analysis revealed that PLR and ECOG-PS were independent predictors of early treatment response.

Conclusion

PLR can be used by clinicians as an effective, inexpensive inflammatory parameter supplementary to the IPI score to predict early treatment response to chemoimmunotherapy. Treatment of patients with DLBCL with high PLR at the time of diagnosis with more potent regimens may be a rational approach for patients to benefit more from treatment.

Purpose

Our objective was to identify whether procalcitonin (PCT) and C Reactive protein (CRP) are useful biomarkers for patients with acute lymphoblastic leukemia/lymphoma (ALL) and febrile neutropenia (FN). We included patients ≥ 15 years of age as existing literature on them is limited.

Methods

In this prospective observational study, high sensitivity CRP (hsCRP) and PCT were estimated for all patients at baseline, 48 hours, and 96 hours after administration of broad-spectrum empirical antibiotics. The level of these parameters was then correlated with bacteremia, requirement of antibiotic augmentation, septic shock, ICU admission, prolonged hospitalisation, and death.

Results

We analysed 33 episodes of FN. Bacteremia was seen in 12% and augmentation of antibiotics was done in 30% of the episodes. Two patients had septic shock; no death or ICU admission was observed. Prolonged hospitalisation was required in 36% of the episodes. The hsCRP and PCT peaked at 48 hours, and the PCT level was significantly higher in the group with bacteremia, antibiotic augmentation, and prolonged hospitalisation. The area under the curve (AUC) for PCT (at 48 hours) was greater than hsCRP for antibiotic augmentation and prolonged hospitalisation.

Conclusion

As a supplement to clinical decision making, serial monitoring of PCT should be done. Levels of PCT at 48 hours of starting antibiotic therapy (≥ 0.82ng/ml) can be used for early augmentation of antibiotic therapy to prevent complications of FN in patient undergoing treatment for ALL.

Background

Pyruvate kinase deficiency (PKD), a rare autosomal recessive disease, often leads to chronic hemolytic complications stemming from mutations in the PKLR gene. Mitapivat, an innovative, allosteric activator of the pyruvate kinase enzyme in red blood cells, has emerged as a potential therapeutic agent. This systematic review aims to meticulously evaluate the efficacy and safety of Mitapivat in treating PKD patients.

Methods

We conducted a comprehensive search across three major databases—PubMed, Web of Science, and Scopus—up to November 2023, utilizing a single-arm meta-analysis methodology.

Results

Our analysis included three clinical trials comprising 94 PKD patients. Hemoglobin (HB) levels improved, with an average increase of 1.05 g/dl (95% Confidence Interval [CI]: -0.22 to 2.33). In terms of hemolysis indicators, there was a notable decrease in indirect bilirubin (mean change: -1.36 mg/dl, 95% CI: -3.67 to 0.95) and an increase in haptoglobin (mean change: 0.26 g/L). Patient-reported outcomes (PROs), assessed via the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Impact Assessment, showed significant improvements, with mean changes of -4.95 (95% CI: -6.711 to -3.19) and − 5.97 (95% CI: -9.87 to -2.06), respectively. Adverse effects were generally mild, with the most common being headache, nausea, elevated alanine aminotransferase, and nasopharyngitis.

Conclusion

Mitapivat substantially improves hemoglobin levels, hemolysis markers, and PROs, maintaining an acceptable safety profile. Nevertheless, additional, larger-scale randomized controlled trials across diverse age groups remain necessary to further corroborate these findings.

Background and Objectives

The expression of the H antigen on red blood cell membranes is dependent on the human FUT1 gene. We herein report a novel FUT1 allele found in a Chinese individual.

Materials and methods

The entire FUT1 genes of these probands were sequenced through PacBio third-generation sequencing. 3D molecular models of the wild-type and mutant fucosyltransferases were generated using the DynaMut web-server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2.

Results

Two probands exhibited discrepancies in their ABO group typing. PacBio sequencing identified that proband 1 possessed a typical ABO*B.01/ABO*O.01.02 genotype for the ABO gene, and was heterozygous with FUT1*01 and a reported functionally weakened allele FUT1*01W.23 (c.424 C > T, p.Arg142Trp) for FUT1 gene. Proband 2 had the ABO*BA.02/ABO*B.01 genotype, and was heterozygous for FUT1*01.02 and a novel FUT1*01-like allele with c.425G > A (p.Arg142Gln). In silico analysis indicated that the c.424 C > T mutation was classified as “Deleterious” or “Damaging”, whereas the c.425G > A mutation was considered “Neutral” or “Benign”.

Conclusion

We have identified a novel FUT1 allele with c.425G > A on the FUT1*01 allele background in an individual exhibiting the B(A) phenotype. These findings contribute to the expanding repository of knowledge regarding the H blood group system.