American journal of blood research最新文献

Background: Limited literature was available on the pattern and determinants of mortality among inborn neonates in comparison to the out born ones. The study's goal was to investigate the patterns and risk factors for mortality among hospitalised, on-ventilator inborn and out born neonates.

Materials and methods: It was an unmatched, case-control, pilot study conducted between January and December 2020 using information retrieved from the medical records of patients attending the neonatal intensive care unit (NICU) of a tertiary healthcare facility, namely Narayan Medical College & Hospital, situated in eastern India.

Results: Congenital pneumonia was the leading cause of death in inborn neonates, with an overall mortality rate of 33.4%. Meanwhile, the overall fatality rate for out born neonates was found to be 43.3%, with birth hypoxia being the most common cause. The only significant attribute affecting mortality in inborn neonates was low arterial blood gas (ABG) pH, whereas in out born neonates they were prematurity, thrombocytopenia, low ABG pO₂, and high pCO₂. Overall, new-borns with thrombocytopenia, low ABG pO₂, and high pCO₂ were observed to be at higher risk for mortality compared to others.

Conclusion: The mortality rate of out born neonates was higher than inborn ones. The attributes affecting mortality were observed to be prematurity, thrombocytopenia, low ABG pH, pO₂, and high pCO₂.

In comparison to the general population, patients with chronic lymphocytic leukemia (CLL) are at a higher risk of developing secondary malignancies. Several factors may contribute to pathogenesis, including direct effects of chemotherapy and radiation as well as the reduction of immune surveillance. Factors influencing the increased risk include the increasing age of CLL patients, chronic antigenic stimulation, and immune impairment related to CLL or chemotherapy. Compared to patients with acute myeloid leukemia (AML) that developed from de novo, therapy-related AML (t-AML) has had a poorer outcome. The range of cytogenetic abnormalities in therapy-related AML is comparable to that in de novo AML, although these patients have a significantly higher frequency of unfavourable cytogenetics, such as a complex karyotype or a deletion or loss of chromosomes 5 and/or 7. Herein, we describe a case of therapy-related AML with monocytic differentiation and t(8;16) with a residual CLL population. The aim of the present case is to highlight rare occurrence of therapy related AML with t(8;16) in CLL after fluderabine based chemotherapy (FCR: fludarabine, cyclophosphamide, and rituximab). This case also highlights flowcytometric immunophenotyping as an ideal tool to characterize secondary AML along with the identification of minimal residual disease of CLL clone, which could have ignored at t-AML diagnosis. The pathogenesis of myeloid and lymphoid malignancies as well as their co-existence can be studied by focusing on such patients. Factors predisposing to the development of t-AML should be studied further, which would help in monitoring these patients more carefully.

The underlying mechanisms and clinical significance of long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is largely unknown in acute myeloid leukemia (AML). We aimed to study the expression of lncRNA UCA1, and its biological and clinical relevance in AML. Expression of lncRNA UCA1 was quantified in peripheral blood (PB) samples of children with de novo AML (n=69), post-induction, after achieving complete remission (CR) (n=8), and in patients who had relapsed (n=10). Additionally, two external cohorts were analysed i.e., TCGA-LAML dataset and Leukemia-MILE study. We also quantified expression in four different AML cell lines and analysed expression after cell differentiation. A consistent pattern of low UCA1 expression in AML was observed in our cohort of sixty-nine patients at baseline (P < 0.0001) and in the TCGA and Leukemia-MILE datasets. In patients who achieved remission, expression was comparable to healthy individuals, while relapsed patients interestingly had lower levels of UCA1 (P=0.0002). Furthermore, lncRNA UCA1 expression was significantly lower in AML cell lines (THP-1, P=0.0112; KG-1, P=0.0168; and HL-60, P=0.0112) and increased when THP-1 cells were differentiated (P=0.0001). In our AML patient cohort, lower expression was significantly associated with CR (P=0.043), however, the impact on survival (EFS and OS) was not significant. This is the first study wherein the lncRNA UCA1 expression was studied in various AML cell lines along with AML patients at baseline, remission and relapse. In conclusion, we found that UCA1 is significantly downregulated in AML compared to healthy individuals and mature differentiated cells.

Bone marrow (BM) is one of the rare but important site of metastasis of solid tumors. The key steps of metastasis include invasion, intravasation, circulation, extravasation, and colonization. Tumor cells may express some adhesion molecules that promote the transmigration to the marrow space and link them to the marrow stroma with subsequent engraftment. It is important to detect the bone marrow metastasis for initial clinical staging, therapeutic selection, prognostic risk stratification, assessment of response to therapy and predicting relapse. Prognosis of non-hematopoietic malignancies with BM metastasis is dismal. Due to occulting and atypical clinical manifestations, bone marrow metastases can be easily missed or misdiagnosed, leading to higher mortality rates. The important factors on which the prognosis of patients with bone marrow metastases depends are primary tumor site, performance status, platelet count, and therapeutic regimens (systemic chemotherapy or palliative/supportive care). Further, in cases with BM metastasis with unknown primary sites, misdiagnosis can lead to delayed initiation of therapy and increased mortality. BM metastasis is seen in less than 10% of patients with metastatic cancer and is common in lung, breast or prostate carcinoma. Bone marrow metastasis can be presented as the initial presentation with hematological changes and may be misdiagnosed as a primary haematopoietic disorder. Leucoerythoblastic blood picture is the most common peripheral blood smear finding indicating BM metastasis, may be an indicator of associated BM fibrosis. Bone marrow aspiration and biopsy with immunohistochemistry (IHC) is an easy, cost effective and gold standard method of detection of BM metastasis. BM biopsy is superior to bone marrow aspirate for detection of metastasis. Morphology of metastatic cells is as per the primary site of tumor. Immunohistochemistry is a useful adjunct to morphology in reaching a definitive diagnosis even in case with carcinoma unknown primary (CUP) and also in diagnosing case of unsuspected malignancies. Though bone marrow is not among the most common site of involvement in CUP, which are liver, bone, lymph nodes and lung. But BM, if involved, the site of origin is determined using the immunohistochemistry panel applied to the metastatic deposits based on the morphology The aim of the review is to discuss the hematological findings of non-haematopoietic malignancies metastasizing to the bone marrow, emphasizing on histomorphology with IHC and its significance in establishing primary diagnosis in clinically unsuspected cases.

Cold agglutinin disease (CAD) is a subgroup of autoimmune hemolytic anemia caused by monoclonal cold agglutinins produced by clonally expanded B lymphocytes. In primary CAD, lymphoproliferative bone marrow disorder is noted, while as one of the secondary cold agglutinin syndromes (CAS), the initial manifestation of CAD is followed by development of lymphoma. Here, we report a case of low-grade B cell lymphoma developed 3 months after an initial CAD diagnosis. The patient had an extremely high serum cold agglutinin titer (1:16,384) and slightly elevated serum IgM (452 mg/dL; reference, 31-200) with positive monoclonal IgM-kappa chain. After diagnosis of lymphoma-associated CAS, he was managed successfully with six cycles of a BR (bendamustine and rituximab) regimen. Cold agglutinin titers fell rapidly to 1:2048 at 5 months and to 1:512 at 10 months after chemotherapy, and the patient has been in a complete remission for 34 months.

Background and aims: The objectives of this study were to investigate the cyto-molecular profile and survival of pediatric acute myeloid leukemia (AML).

Methods: This prospective study was carried out in a tertiary care hospital from October 2018 to December 2020. Karyotype and cytogenetics analyses were done to identify chromosomal aberrations in pediatric AML. The targeted molecular panel utilized the polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), and fragment analysis.

Results: A total of 70 patients of AML with aged ≤18 years were enrolled in this study. The cytogenetic analyses revealed abnormal/recurrent cytogenetic abnormalities (CA) in 64.3% of patients and normal cytogenetics (CN) in 35.7% of patients. FAB M2 subtype showed frequent aberrant expression of the CD19 marker. CD7, CD11b, and CD36a were significantly present in the absence of molecular markers. Common chromosomal abnormalities were t(translocation) (8;21) (55%), monosomy/deletion 7 (13%), monosomal karyotype (5%) and complex karyotype (3%). The fusion transcripts RUNX1-RUNX1T1 [t(8;21)] (41%) and CBFB-MYH11 [t(16;16)] (3%) were detected by RT-PCR and FLT3-TKD D835 mutation (1.5%) by allele-specific oligo PCR. Fragment analysis revealed NPM1 (8%) mutation and FLT-ITD (9.5%) mutations. Complete remission was achieved in all evaluable patients. The median follow-up period of our patients was 225 days (IQR 28; 426 days). The median event-free survival (EFS) in all patients was 11.9 months (95% CI, 5-12.6 months). The forty months overall survival probability (pOS) was 58% in all patients.

Conclusion: The majority of patients had abnormal/recurrent cytogenetics abnormalities. FAB M2 subtype showed frequent aberrant expression of the CD19. The absence of molecular markers may suggest the presence of CD7, CD11b, and CD36a expression. The overall survival has increased considerably in LMIC.

Hypocellular AML being a rare entity with considerable overlapping features and characteristics with various other entities brings a need to have a better and clear understanding of hypocellular AML to differentiate in the decision-making process for therapeutic patient management. With some degree of dysplasia inherently associated with AML it is challenging to differentiate hypocellular AML from Myelodysplastic syndromes. We present a case report where the diagnostic dilemma in an elderly male patient who presented with fever, pallor, weight loss and fatiguability. On clinical examination, the patient had hepatomegaly. The patient was non-affording and was hence given supportive treatment, and he died soon after. Here the diagnostic dilemma is discussed along with the review of literature on hypocellular AML. A better and clear understanding of hypocellular AML is required to differentiate it from other entities due to the considerable overlap in presentation hence improving the decision-making process for therapeutic patient management. The shortcomings are realised, especially when the bone marrow cellularity is less than 10%. Our case report is written to enrich more understanding of the limited published literature on the subject.

Background: Immune thrombocytopenia (ITP) has been shown to be independently associated with aortic valve disease (AVD). However, whether ITP patients who have undergone splenectomy are also at increased risk for AVD has not been researched. The goal of this study was to evaluate any association between AVD and splenectomy in patients with ITP.

Method: We used the Nationwide Inpatient Sample from 2005 to 2014 as 10 consecutive years randomly selected. Using ICD-9 codes for AVD, ITP, and splenectomy, a total of 108,434 patients were identified with ITP, 4,282 of which had undergone splenectomy. We performed uni- and multivariate analysis adjusting for baseline characteristics.

Results: Univariate analysis revealed a significantly lower rate of AVD in ITP patients with splenectomy compared to no splenectomy in 2007, 2009, and 2010 with a trend of this association during the other years. For example, in 2007, 0.6% of ITP patients with history of splenectomy had AVD versus 2.0% of ITP patients without splenectomy (OR, 0.29; 95% CI, 0.09-0.91; P = 0.02). Similarly, in 2010, 0.2% of ITP patients with history of splenectomy had AVD versus 1.9% of ITP patients without splenectomy (OR, 0.13; 95% CI, 0.02-0.92; P = 0.02). After adjusting for age, gender, race, diabetes, hypertension, hyperlipidemia, and tobacco use, we confirmed that ITP patients with splenectomy have no association with prevalence of aortic valve disease (2005: OR, 0.48; 95% CI, 0.18-1.30; P = 0.15; 2014: OR, 0.88; 95% CI, 0.36-2.16; P = 0.77).

Conclusion: Based on a large inpatient database, our previous finding of ITP patients' association with AVD is only present in patients without splenectomy, and splenectomy appears to exert a protective effect on developing aortic valve disease in ITP patients, warranting further investigation.

Background: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of diffuse large B-cell lymphoma seen in immunocompromised individuals. It has a diffuse growth pattern, with no standard therapy and a poor survival rate. Due to overlap in presenting features with lymphoma and myeloma, PBL is often a diagnostic dilemma. We present a case of PBL in a young immunocompetent female who developed treatment associated complications.

Case report: A 36-year-old presented with a lesion extending from the oral cavity to the pharynx and involving the angle of the mandible. Radiology and laryngoscopy described a growth pattern that was diagnosed to be PBL on histopathology. The patient underwent chemotherapy using level II DA-EPOCH (dose-adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and prophylactic granulocyte-colony stimulating factor along with radiotherapy and ultimately, achieved metabolic response. However, she developed several episodes of paralytic ileus, cytopenia, oral ulcers, dermatitis and long-standing hypothyroidism as therapy-related complications and has been on treatment for the same ever since.

Conclusions: Thus, a high index of suspicion is necessary for early diagnosis and rapid initiation of therapy. Further, there is a need to detect and address therapy related complications early to prevent long-standing, therapy-related side effects from developing and deteriorating the patient's quality of life.

Beta thalassemia is associated with decreased immunity possibly due to iron overload. Al-hijamah (Hijamah) is wet cupping therapy (WCT) of prophetic medicine. Prophet Muhammad Peace be upon him said: "The best among your treatments is Al-hijamah". Al-hijamah is a promising excretory treatment to clear blood of causative pathological substances. Al-hijamah is a three-step technique (skin suction, scarification and suction) i.e. triple S technique). Recently, we introduced Al-hijamah as a novel iron excretion therapy (through pressure-dependent filtration then excretion via the skin dermal capillaries) that significantly decreased serum iron overload and related oxidative stress using a physiological excretory mechanism (Taibah mechanism). Iron overload was reported to impair both humoral immunity and cell mediated immunity in patients with beta thalassemia. In this study, twenty patients having β-thalassemia major (maintained on iron chelation therapy) underwent a single session of Al-hijamah (30-60 minutes) using 4-5 sucking cups only. Another age and sex-matched control group of thalassemic patients received iron chelation therapy only. Al-hijamah enhanced the immunity of thalassemic patients in the form of increased CD4⁺ T cell count, from 124.10±36.98 to 326.20±57.94 cells/mm³, and an increased CD8⁺ T cell count from 100.30±36.98 to 272.40±46.37 cells/mm³. CD4/CD8 ratio significantly increased from 1.29 to 1.7 (P<0.001). There was a significant increase of ten times (P<0.001) in serum TAC/MDA ratio (reflects increased antioxidant capacity vs decreased oxidative load and stress) induced by Al-hijamah. After Al-hijamah, both CD4⁺ and CD8⁺ T cell counts significantly increased and positively correlated with TAC/MDA ratio (r = 0.246) and (r = 0.190), respectively. Moreover, CD4/CD8 ratio positively correlated with TAC/MDA after Al-hijamah (r = 0.285). In conclusion, Al-hijamah significantly increased CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio. Our study strongly recommends medical practice of Al-hijamah in hospitals for its immune potentiating effects in agreement with the evidence-based Taibah mechanism. Al-hijamah should be generalized for treating other immune-deficiency conditions. Al-hijamah-induced bloody excretion is so minimal and never aggravates the anaemic status.