Search

The reasons for progression and autoimmune cytopenias (AIC) in chronic lymphocytic leukemia (CLL) are not entirely clear, with previous studies suggesting a role for regulatory T-cells (Treg). In this study we prospectively studied Treg (CD3 + CD4+ CD25highCD127low), interleukin-10 (IL-10) producing Treg and T-helper 17 (Th17) (CD3 + CD4+ IL-17+) cells in 40 treatment-naive patients with CLL. The percentage of Th17 and not Treg cells was significantly higher in the AIC cohort than in those without AIC (p< 0.0001). The Treg:Th17 ratio was skewed in favor of Th17 in the AIC cohort (p= 0.02). Th17 cells are responsible for AIC of CLL. Analysis of lymph-node aspirates showed that the percentage of Treg and IL-10 expression in Treg and not Th17 was significantly higher than in peripheral blood (p< 0.01). Treg cells play a major role in the microenvironment where disease progression occurs. This shows the importance of maintaining the Treg:Th17 equilibrium, for imbalance leads to CLL progression or AIC. [ABSTRACT FROM PUBLISHER]

Regulatory T-cells (Tregs) have been shown to be important for the balance of autoimmunity and oncogenesis. Tregs have a protective role in autoimmune diseases and conversely promote oncogenesis. Chronic lymphocytic leukemia (CLL) is unique in being at the cross-roads of oncogenesis and autoimmunity. We studied Tregs, defined as CD4+CD25highCD127lowFOXP3+, in 32 treatment-naive patients with CLL. Our study shows that patients with CLL had a higher absolute Treg count than the control group ( p < 0.001). A progressive increase of Tregs was noted in advanced stages of the disease ( p < 0.001). The increase in absolute Treg count is more significant than the increase in percentage Tregs. The absolute Treg count appears to be more important in disease pathogenesis. The absolute Treg count was significantly higher in those patients having autoimmune cytopenias. There was an inverse correlation between lymphocyte doubling time and absolute Treg count ( p = 0.03). The absolute Treg count may be used as a prognostic marker in CLL. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) has been reported to be associated with the occurrence of autoimmune disorders, including immune thrombocytopenic purpura (ITP). This has suggested that HCV could be responsible for thrombocytopenia in these patients. This study was performed to estimate the frequency of HCV infection in patients of chronic ITP (cITP), and to find the frequency of thrombocytopenia in chronic HCV infection. Materials: A total of 150 subjects were included in the study. Fifty consecutive adult patients with cITP (< 6 months'' duration) and 50 age-matched patients with chronic HCV were included for comparison of platelet counts in two groups. Fifty age-matched healthy subjects were also included in the control group. All patients'' sera were tested for the presence or absence of HCV-RNA. Anti-HCV antibodies were tested in patients as well as in controls. Complete blood count and examination of peripheral blood smear were done followed by bone-marrow aspiration to confirm the diagnosis of ITP. Results: Three patients (6%) were tested positive for anti-HCV antibodies while no subject was positive in control group (P=0.24). The prevalence of severe thrombocytopenia (platelet counts <50,000/mL) was significantly higher in ITP patients compared with that in chronic HCV patients (P=0.0001). Thrombocytopenia occurred more frequently in patient with moderate to severe than mild stage of fibrosis (P=0.001). Conclusion: In conclusion, thrombocytopenia in ITP patients was not associated with HCV infection. The prevalence of thrombocytopenia was more common and more severe in ITP patients when compared with that in patients with chronic HCV. Thrombocytopenia in chronic HCV patients was related to the stage of fibrosis and to the duration of HCV infection. [ABSTRACT FROM AUTHOR]

Cure rates for adult acute lymphoblastic leukemia (ALL) in developing countries are significantly lower because of problems unique to these countries. We assessed some of the problems in adult ALL patients (>12 years of age) in a tertiary care hospital of northwest India with modified BFM regimen. The diagnosis of ALL was made according to FAB criteria. The protocol consisted of Phase I & II induction, consolidation, reinduction and maintenance phases. CNS prophylaxis was administered with 24 Gy radiation and intrathecal methotrexate. One hundred and eighteen patients (72.9% males), aged 12 - 68 years (median 23 years) were treated from January 1997 till December 2003. Follow-up of patients was done till December 2005. Complete remission (CR) was achieved in 85.6% patients after induction therapy and 40% patient relapsed. Most patients (23.7%) relapsed during the maintenance phase or after completion of chemotherapy. At least 15% of patients (15/101) after successful induction abandoned the treatment because of financial constraints, prolonged travel time to treatment facility and switching over to alternative medicines. Fatal infectious complications occurred in 19.5% of patients. The 3-year and 5-year event free survival rates were 29.8% and 21.6% respectively. In conclusion, modified BFM regimen resulted in high induction rates but relatively poor 5-year event free survival. Infections related death and post induction abandonment of treatment were the main reasons for poor overall results. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin (IVIg) is emerging as the mainstay in the treatment of many autoimmune diseases, including systemic lupus erythematosus. IVIg has been found to be beneficial in myocarditis due to dermatomyositis/polymyositis, Kawasaki disease, and viral myocarditis in children. We report an 18-year-old man of active lupus with worsening cardiac systolic function who did not respond to pulse methylprednisolone and cyclophosphamide, but subsequently showed an improvement in his cardiac function after IVIg administration. [ABSTRACT FROM AUTHOR]

Background: Philadelphia chromosome (Ph)–like B‐acute lymphoblastic leukemia (B‐ALL) is a clinically significant, high‐risk genetic subtype of B‐ALL cases. There are few data on the incidence, characterization, and treatment outcomes of Ph‐like ALL cases from low‐ and middle‐income countries. There is a pressing need to establish a well‐organized/cost‐effective approach for identifying Ph‐like ALL instances. Methods: Multiplex reverse transcriptase polymerase chain reaction, nCounter NanoString, and fluorescence in situ hybridization were used to detect and characterize Ph‐like ALL cases among recurrent genetic abnormalities (RGA)neg B‐ALL cases. At the end of induction therapy, flow cytometry‐minimal residual disease (MRD) assay was used to quantify MRD positivity in Ph‐like ALL cases. Results: Of 130 newly diagnosed B‐ALL cases, 25% (BCR::ABL1), 4% (ETV6::RUNX1), 5% (TCF3::PBX1), 2% (KM2TA::AFF1), and 65% RGAneg B‐ALL cases were revealed by multiplex reverse transcriptase polymerase chain reaction. Among RGAneg B‐ALL cases, 24% Ph‐like ALL cases using nCounter NanoString were identified, with 48% CRLF2high cases with 45% CRLF2::P2RY8 and 18% CRLF2::IGH rearrangements(∼r) revealed by fluorescence in situ hybridization. In 52% of CRLF2low cases, 17% ABL1 and JAK2∼r 8% EPOR::IGH & PDGRFB∼r were identified. Ph‐like ALL cases had higher total leukocyte count (p <.05), male preponderance (p <.05), and high MRD‐positivity/induction failure compared with RGAneg B‐ALL cases. Furthermore, in Ph‐like ALL cases, 11 significant genes using quantitative polymerase chain reaction were identified and validated. CRLF2, IGJ, CEACAM6, MUC4, SPATS2L and NRXN3 genes were overexpressed and show statistical significance (p <.05) in Ph‐like ALL cases. Conclusions: This study showed the high incidence of Ph‐like ALL cases with kinase activating alterations and treatment outcomes from low‐ and middle‐income region. Furthermore, a surrogate cost‐effective multiplex panel of 11 overexpressed genes for the prompt detection of Ph‐like ALL cases is proposed. Plain Language Summary: Identification of recurrent gene abnormalities (RGA)neg B‐acute lymphoblastic leukemia (B‐ALL) cases using multiplex‐reverse transcriptase polymerase chain reaction.Identification and characterization of Philadelphia (Ph)–like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization.Furthermore, Ph‐like ALL cases were characterized according to CRLF2 expression and kinase‐activating genomic alterations. Minimal residual disease of Ph‐like ALL cases were quantified using flow cytometry‐minimal residual disease assay.A surrogate molecular approach was established to detect Ph‐like ALL cases from low‐ and middle‐income countries. A surrogate approach for the rapid baseline detection of Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia cases, followed by its kinase gene alterations. Early detection of Ph–like acute lymphoblastic leukemia cases is extremely important to start personalized treatments to improve the overall survival/outcomes of these cases. [ABSTRACT FROM AUTHOR]

Gene expression profiling is the criterion standard for recognizing Ph-like ALL signatures among B-ALLs. The prerequisite of GEP is the accurate normalization of target genes with stable expression of housekeeping genes in a quantitative PCR. HKGs exhibit differential expression in the different experimental conditions and affect the target genes' expression, leading to imprecise qPCR results. The selection of stable HKGs is crucial in GEP experiments, especially in identifying high-risk Ph-like ALL cases. We have evaluated the expression stability of nine HKGs (GAPDH, ACTB, GUSB, RNA18S, EEF2, PGK1, B2M, TBP and ABL1) in identified Ph-like ALLs and Ph-negative (n = 23 each) using six algorithms, 4 traditional softwares; geNorm, BestKeeper, NormFinder, Delta Cq value method, and two algorithms, RefFinderTM and ComprFinder. Further, we have validated the expression of 8 overexpressed normalized genes in Ph-like ALL cases (JCHAIN, CA6, MUC4, SPATS2L, BMPR1B, CRLF2, ADGRF1 and NRXN3). GeNorm, BestKeeper, NormFinder, Delta Cq value method, RefFinderTM and ComprFinder algorithm analysis revealed that EEF2, GAPDH, and PGK1 form the best representative HKGs in Ph-like ALL cases, while RNA18s, ß-actin, and ABL1 in Ph-negative ALLs. Lastly, we performed a correlation analysis and found that the combination of EEF2, GAPDH, and PGK1 represents the best combination with a very high correlation in Ph-like ALL cases. This is the first report that shows EEF2, GAPDH, and PGK1 are the best HKG genes and can be used in the diagnostic panel of Ph-like ALL cases using qPCR at baseline diagnosis. [ABSTRACT FROM AUTHOR]

Background: The published literature on hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low‐income countries. For newer classifications such as BCR::ABL1‐like ALLs, the scarcity of patient‐level data is even more pronounced. Methods: The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1‐like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1‐like ALL subtype and other genetic subtypes of ALL. Results: Patients with BCR::ABL1‐positive and BCR::ABL1‐like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1‐negative cases (p <.05). Logistic regression modeling of B‐lineage‐ALL (B‐ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1‐like ALL (p <.05). Furthermore, patients with BCR::ABL1‐like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1‐negative ALLs (p <.05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1‐like ALLs compared to BCR::ABL1‐negative ALL cases (p <.05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1‐positive ALL cases were statistically significant (p <.05), and BCR::ABL1‐like ALL cases had high MRD‐positivity as compared to BCR::ABL1‐negative ALL cases but did not show statistical significance. Conclusions: The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B‐ALLs. This is the first report characterizing the hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. Plain Language Summary: Characterizing the hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India.We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs.Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1‐like ALL cases compared to BCR::ABL1‐negative ALL cases.Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1‐like ALLs (p <.05).In terms of treatment outcomes, BCR::ABL1‐positive ALL had statistically significant minimal residual disease (MRD) (p <.05), and BCR::ABL1‐like ALL cases had high MRD‐positivity but did not show statistical significance as compared to BCR::ABL1‐negative ALLs. This study characterizes prognostically significant genetic subtypes of B‐acute lymphoblastic leukemia (B‐ALL). Logistic regression modeling of cluster of differentiation markers and clinical symptoms is used to predict various genetic subtypes of B‐ALL. [ABSTRACT FROM AUTHOR]

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/μL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/μL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/μL (range 1000–19000/μL) and 8000/μL (range 1000–19000/μL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 54 years old woman who was diagnosed with skin necrosis related to warfarin.

The article presents a case study of 16-year-old boy presented with epistaxis and petechial spots on the body. Topics discussed include low platelet counts revealed in laboratory examination, megakaryocytic thrombocytopenia revealed in examination of bone marrow, and prescription of danazol and azathioprine after prednisolone. It mentions that radiological investigations including magnetic resonance and venography revealed venous thrombosis of left transverse and sigmoid sinus.

The article describes the case of a 62 year old female patient suffering from multiple myeloma. Topics discussed include the medical history of the patient, confirmation of the diagnosis of herpes zoster with Tzanck smear that showed multinucleated giant cells, the patient's failure to take acyclovir prophylaxis during chemotherapy and increased susceptibility of patients on bortezomib to herpes infection.

Background: Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post‐AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. Materials and methods: We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient‐specific, disease‐specific, and transplant‐specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen‐related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. Results: Ninety‐five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33–68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4–144). Eighty‐nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile‐associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9–14) and 12 days (range 9–23), respectively. The median duration of hospital stay was 16 days (range 9–29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant‐related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression‐free survival of the study population at 5 years were 72.7% and 64.8%, respectively. Conclusion: This study shows that the incidence of infections and TRM are higher in MM patients from lower‐middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Early detection of BCR::ABL1-like ALL could impact treatment management and improve the overall survival/outcome. BCR::ABL1-like ALL cases are characterised by diverse genetic alterations activating cytokine receptors and kinase signalling. Its detection is still an unmet need in low–middle-income countries due to the unavailability of a patented TLDA assay. Methods: This study's rationale is to identify BCR::ABL1-like ALLs using the PHi-RACE classifier, followed by the characterisation of underlying adverse genetic alterations in recurrent gene abnormalities negative (RGAneg) B-ALLs (n = 108). Results: We identified 34.25% (37/108) BCR::ABL1-like ALLs using PHi-RACE classifier, characterised by TSLPR/CRLF2 expression (11.58%), IKZF1 (Δ4–7) deletion (18.9%) and chimeric gene fusions (34.61%). In overexpressed TSLPR/CRLF2 BCR::ABL1-like ALLs, we identified 33.33% (1/3) CRLF2::IGH and 33.33% (1/3) EPOR::IGH rearrangements with concomitant JAK2 mutation R683S (50%). We identified 18.91% CD13 (P = 0.02) and 27.02% CD33 (P = 0.05) aberrant myeloid markers positivity, which was significantly higher in BCR::ABL1-like ALLs compared to non-BCR::ABL1-like ALLs. MRD positivity was considerably higher (40% in BCR::ABL1-like vs. 19.29% in non-BCR::ABL1-like ALLs). Conclusions: With this practical approach, we reported a high incidence of BCR::ABL1-like ALLs, and a lower frequency of CRLF2 alteration & associated CGFs. Recognising this entity, early at diagnosis is crucial to optimise personalised treatment strategies. [ABSTRACT FROM AUTHOR]

Aim Kawasaki disease ( KD) is the most common cause of acquired heart disease in children in Japan, North America and Europe. Undiagnosed and untreated KD can have clinically significant consequences later in life. The clinical spectrum of missed childhood KD is frequently being recognized during adulthood. We report four adult cases of acute coronary events, in which coronary angiography was suggestive of sequelae of KD. Methods Four adults who presented with acute coronary events, had coronary angiography for evaluation. Indoor-admission files were analyzed for the clinical details of individual cases. Results Two cases were below 40 years of age. None of the patients had any known conventional risk factors for atherosclerosis. Case 4 had a clinical history of childhood KD. Coronary angiography revealed ectasia of multiple coronary arteries and stenosis in distal segments in the first three cases and large thrombosed aneurysm with calcified walls in the fourth case. Conclusion We hereby report four adult cases with acute coronary events, who had markedly dilated coronary artery segments suggestive of possible sequelae of childhood KD. [ABSTRACT FROM AUTHOR]

Background: The gold standard for the identification of Philadelphia (Ph)‐like acute lymphoblastic leukemia (ALL) patients is gene expression profiling. Because of its diverse nature, its identification is extremely difficult and expensive. On the genomic and proteomic landscape of Ph‐like ALL patients, there is a paucity of published literature from developing countries. Methods: The authors used digital barcoded nCounter NanoString gene expression profiling for its detection, followed by molecular and proteomic characterization using fluorescence in situ hybridization and liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: The authors found 32.05% Ph‐like ALL patients and their median age at presentation was considerably higher than Ph‐negative ALL cases (p =.0306). Furthermore, we identified 20% CRLF2 overexpressed cases having 8.33% CRLF2‐IGH translocation with concomitant R683S mutation and 8.33% CRLF2‐P2RY8 translocation. In 80% of CRLF2 downregulated cases, we identified 10% as having JAK2 rearrangement. Minimal residual disease‐positivity was more common in Ph‐like ALL cases (55.55% vs. 25% in Ph‐negative ALL cases). Immunoglobulin J chain (Jchain), small nuclear ribonucleoprotein SmD1 (SNRPD1), immunoglobulin κ constant (IGKC), NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 2 (NDUFA2), histone H2AX (H2AFX), charged multivesicular body protein 4b (CHMP4B), and carbonyl reductase (NADPH) (CBR1) proteins were identified to be substantially expressed in Ph‐like ALL patients, using LC–MS/MS. Gene enrichment analysis indicated that involvement of spliceosomal mediated messenger RNA splicing pathway and four microRNAs was statistically significant in Ph‐like ALL patients. Conclusions: For the first time, we have described incidence, molecular, and proteomic characterization of Ph‐like ALL, in developing nations. Plain language summary: In developing countries, detecting Philadelphia (Ph)‐like B‐lineage acute lymphoblastic leukemia is complicated and challenging due to its diverse genetic landscape.There is no well‐defined and cost‐effective methodology for its detection.The incidence of this high‐risk subtype is very high in adult cases, and there is an urgent need for its accurate detection.We have developed an online PHi‐RACE classifier for its rapid detection, followed by delineating the genomic and proteomic landscape of Ph‐like acute lymphoblastic leukemias for the first time in Indian patients. The identification of Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia (ALL) cases with NanoString nCounter digital‐barcoded gene expression profiling was examined in Indian patients. A higher incidence of Ph‐like ALL cases (32.05%) was identified. Furthermore, genomic and proteomic characterization of Ph‐like ALL cases was performed in Indian patients. This is the first report on the incidence and characterization of Ph‐like ALL cases from developing nations. [ABSTRACT FROM AUTHOR]

Summary: Arsenic trioxide (ATO) and all‐trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high‐risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate‐ and high‐risk disease received a further 2 years of maintenance with ATRA, 6‐mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow‐up. The mean (SD) estimated 5‐year event‐free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5‐year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long‐term outcomes in the real‐world setting. [ABSTRACT FROM AUTHOR]

Background & objectives: Adriamycin though considered as an effective anticancer drug, leads to irreversible cardiomyopathy (CMP) and congestive heart failure (CHF). The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy (CMP) in cancer patients. Methods: Patients with lymphoreticular malignancy in whom ADR therapy was planned were randomized into two groups: carvedilol and control. Twenty seven patients each were enrolled in carvedilol and control groups. In the carvedilol group, 12.5 mg once daily oral carvedilol was given during six months. The patients were evaluated by echocardiography before and after chemotherapy. Left ventricular ejection fraction (EF) and systolic and diastolic diameters were calculated. Results: At six months of follow up, six patients in the carvedilol group and five in the control group had died. The mean EF (63.19 vs. 63.88%) and fraction shortening (FS) (34 vs. 34.6) of the carvedilol group were similar at follow up, but in the control group, the mean EF (67.27 vs. 60.82%, P=0.003) and FS (38.48 vs. 34.6, P<0.05) at control echocardiography were significantly lower. In carvedilol group, both systolic and diastolic diameters were not changed, but in control group, systolic diameters were significantly increased compared with basal measures (left ventricular end systolic diameter = 28.26±5.50 mm vs. 31.25± 6.50 mm; P< 0.05). Interpretation & conclusions: Prophylactic use of carvedilol in patients receiving anthracycline protected systolic functions of the left ventricle. Carvedilol can be a potential drug which can ameliorate ADRinduced CMP. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Chronic myeloid leukaemia," by R. Hehlmann, S. Hochhaus and M. Baccarani in the July 28, 2007 issue.

The article describes the case of a 61-year-old male patient with a history of CD20 positive follicular non-Hodgkin's lymphoma, blisters and skin lesions with pruritus, and who was diagnosed with paraneoplastic pemphigus (PNP) which was treated with rituximab. The patient was subjected to Tzank smear, histopathological examination, immunofluorescence and ski biopsy. A discussion on the presence of anti-Dsg3 in PNP is offered.

For the detection of BCR-ABL1-like ALL cases, two methodologies, specifically Gene expression profiling (GEP) or Next-generation targeted sequencing (NGS) and TaqMan based low-density (TLDA) card, are being used. NGS is very costly and TLDA is not widely commercially available. In this study, we quantified the expression of 8 selected overexpressed genes in 536 B-ALL cases. We identified 26.67% (143/536) BCR-ABL1-like ALLs using hierarchical clustering and principal component analysis. BCR-ABL1-like ALL cases were significantly older at presentation (p = 0.036) and had male preponderance (p = 0.047) compared to BCR-ABL1-negative ALL cases. MRD-positivity and induction failure were more commonest in BCR-ABL1-like ALL cases (30.55 vs.19.35% in BCR-ABL1-negative ALL cases). Lastly, we built a PHi-RACE classifier (sensitivity = 95.2%, specificity= 83.7%, AUC= 0.927) using logistic regression to detect BCR-ABL1-like ALL cases promptly at diagnosis. This classifier is beneficial for hematologists in quick decision making at baseline to start tailored treatment regimes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a patient diagnosed with myeloid sarcoma (MS) with chronic myeloid leukemia (CML) after being presented as shoulder pain that mimics septic arthritis.

The article focuses on a study which described the safety and efficacy of high-dose hydroxyurea (HDH) for cytoreduction in acute promyelocytic leukemia (APL). Ultra-high-risk patients with APL were analyzed between 2016 and 2021. It was observed that study participants who received HDH has lower early mortality and that none of them developed mucositis. Overall survival of the patients were compared using the Kaplan-Meier technique.

Objective: Based on the immunophenotype, acute lymphoblastic leukemia (ALL) can be categorized into B-cell or T-cell lineages. B-cell precursor ALL (BCP-ALL) cases show various genetic/molecular abnormalities, and varying frequencies of chimeric fusion transcripts in BCP-ALL cases are reported from different parts of the world. We studied the immunophenotypic aberrancy profiles of a large number of BCP-ALL cases with respect to various common chimeric fusion transcripts. Materials and Methods: Flow cytometric immunophenotyping and multiplex reverse-transcription polymerase chain reaction assays were performed for 986 BCP-ALL cases. Results: Among 986 BCP-ALL cases, the incidence of various fusion transcripts was 38.36% in adult cases and 20.68% in pediatric cases. Adult BCP-ALL patients with t(9;22)(BCR-ABL1) fusion transcripts and expression of aberrant myeloid markers were significantly older at presentation (p=0.0218) with male preponderance (p=0.0246) compared to those without aberrant myeloid expression. In pediatric patients with the t(12;21)(ETV6-RUNX1) chimeric fusion transcript, aberrant expression of CD13 was observed in 39.13%, CD33 in 36.95%, and CD117 in 8.69% of patients, respectively. Pediatric BCP-ALL patients with the ETV6-RUNX1 fusion transcript and expression of aberrant myeloid markers were not significantly different compared to those without with respect to demographic and clinical/hematological characteristics (p=0.5955). Aberrant myeloid markers were rarely or never expressed in pediatric and adult BCP-ALL patients with the t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts. Conclusion: Aberrant myeloid markers were frequently expressed among BCP-ALL patients with the t(9;22)(BCR-ABL1) and t(12;21) (ETV6-RUNX1) fusion transcripts. However, BCP-ALL patients with the t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts rarely or never expressed aberrant myeloid markers. Aberrant myeloid CD markers can be used in predicting chimeric fusion transcripts at baseline so as to plan appropriate tyrosine kinase inhibitor therapy in cases of BCP-ALL with specific chimeric fusion transcripts. This study has delineated the relationship of chimeric fusion transcripts with the aberrant expression of myeloid markers in a large cohort of BCP-ALL cases. [ABSTRACT FROM AUTHOR]

We report a case of AML in a 29-year-old HIV-positive female on anti-retroviral therapy. She presented with bicytopenia, fever and easy fatiquability. Bone marrow examination revealed 77% blasts, which on flow cytometric immunophenotyping showed positivity for myeloid lineage markers and were negative for monocytic and lymphoid lineage markers. Although rare, AML is seen in HIV patients, therefore, in presence of persistent cytopenias, detailed hematological evaluation should be done so as to not miss/delay the AML diagnosis. [ABSTRACT FROM AUTHOR]

Background & objectives: Chronic myelogenous leukaemia (CML) is the commonest leukaemia in Asia. There is a paucity data on cytogenetic and molecular analyses of Indian CML patients. This apparently reflects the low availability of cytogenetic and molecular techniques in our country. This study aimed to document various types of BCR-ABL fusion transcripts in different phases of CML and to compare the Ph chromosome positivity/negativity vis-a-vis BCR-ABL fusion transcripts in adult CML patients. Methods: Between June 2004 and February 2009, 208 patients were diagnosed as CML in chronic phase (CP), accelerated phase (AP) and blast crisis (BC), according to standard criteria. Cytogenetic and molecular genetic analyses were performed in all patients. Various types of BCR-ABL hybrid transcripts were compared with phases of CML and cytogenetic abnormalities. Results: Among 208 CML patients, b3a2 BCR-ABL transcripts were most commonly detected (66.82%) followed by b2a2 (28.84%), b3a2 + b2a2 (3.36%), b3a2 + e19a2 (0.48%) and b2a2 + e19a2 (0.48%). b3a2 transcripts were more frequently detected than b2a2 transcripts, in the whole group of 208 as well as in 183 CML-CP patients (P<0.0001). Ph chromosome was positive in 135 of 139 patients with b3a2 transcripts and 56 of 60 patients with b2a2 transcripts, difference not being significant. Additional cytogenetic abnormalities detected in 3.8 per cent patients in CML-CP and 44 per cent patients in CMLAP/ BC, did not show predilection for any BCR-ABL transcript type. Interpretation & conclusions: This study documents higher Ph positivity (96.15%) by cytogenetic analysis among CML patients, as confirmed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in a large patient group from north India. Both the techniques contribute towards understanding the disease biology, and have important implications for diagnosis and management of CML patients. [ABSTRACT FROM AUTHOR]

Most cases of leukemia show hTERT and WT1 gene overexpression. However, the role of these genes in the progression and monitoring of chronic myeloid leukemia (CML) has not been very well explored. Two hundred and eight patients diagnosed as having CML in chronic phase (CP), accelerated phase (AP), and blast crisis (BC) were studied. Real-time polymerase chain reaction (PCR) was performed for comparative quantification of BCR--ABL, hTERT, and WT1 gene expression. The expression levels of the three genes were compared among the three phases and seven imatinib-naive and -treated subgroups. Among the three major groups, the gene expression levels of hTERT ( p < 0.01) and WT1 ( p < 0.01) were significantly different. Freshly diagnosed, imatinib-responsive, and -unresponsive patients among these revealed interesting changes in hTERT and WT1 gene expression profiles, especially in 25 patients with CML in whom sequential samples were analyzed. Our results showed that hTERT and WT1 gene expression analyses provided relevant information for the understanding of disease progression and indicate their possible usefulness as surrogate markers for treatment monitoring. [ABSTRACT FROM AUTHOR]

Background: Acute onset fever with altered mentation is a common problem encountered by the physician practicing in tropical countries. Central nervous system (CNS) infections are the most common cause resulting in fever with altered mentation in children. Aim: In this study, we have tried to analyze the cause of encephalopathy following short febrile illness in adults presenting to a tertiary care center in Northwestern part of India. Setting and Design: A prospective observational study carried out in a tertiary care center in the Northwestern India over a period of 1 year. Material and Methods: A total of 127 patients with fever of less than 2 weeks duration along with alteration in mentation were studied prospectively over a period of 12 months. The demographic variables were recorded in detail. In addition to routine investigations, cerebrospinal fluid analysis, noncontrast- and contrast-enhanced computed tomography, along with magnetic resonance imaging were performed in all the subjects. Statistical Analysis: The results were analyzed using SPSS statistical software. The values were expressed as mean with standard deviation for contiguous variable as percentage for the others. Results and Conclusion: Out of these, 70% had primary CNS infection as the etiology. A total of 33% patients had meningitis, 29.9% had evidence of meningoencephalitis, and 12.7% were diagnosed as sepsis-associated encephalopathy. These were followed by cerebral malaria, leptospirosis, and brain abscess as the cause of febrile encephalopathy in adults. Among the noninfectious causes, acute disseminated encephalomyelitis, cortical venous thrombosis, and neuroleptic malignant syndrome were documented in 2.36% each. In 11% of the patients, the final diagnosis could not be made in spite of the extensive investigations. Our study demonstrates that acute febrile encephalopathy in adults is a heterogeneous syndrome with primary CNS infections being the commonest etiology. [ABSTRACT FROM AUTHOR]

Background: Amoebic Liver abscess although fairly common in developing countries, yet, there is limited data on the clinical presentation to the emergency department. A retrospective analysis of 86 indoor cases of Amoebic Liver Abscess presenting to the emergency department over a 5-year period was carried out. Findings: The mean age of patients was 40.5 ± 2.1 years (male-female ratio = 7:1). Fever, pain abdomen and diarrhea were seen in 94%, 90% and 10.5% respectively. Duration of symptoms less than 2 weeks was seen in 48% cases. Hepatomegaly was present in 16% cases only, a right sided pleural effusion in 14% cases and ascites in 5.7%. On ultrasound, a right lobe abscess was seen in 65%, a left lobe abscess in 13% and multiple abscesses in both the lobes in 22% cases. Seventy one cases underwent per-cutaneous pigtail catheter drainage for a mean period of 13.4 ± 0.8 days. The mortality rate was 5.8%. On multivariate regression and correlation analysis, a higher number of inserted pigtail catheters correlated to mortality. Conclusions: Amoebic liver abscess presents commonly to the emergency department and should be suspected in persons with prolonged fever and pain abdomen. Conservative management for uncomplicated amoebic liver abscess and insertion of single per-cutaneous pigtail catheter drainage for complicated amoebic liver abscess are efficacious as treatment modalities. [ABSTRACT FROM AUTHOR]

A uniform protein profile of bands at 34, 43, and 52 kDa was obtained with all the cerebrospinal fluid (CSF) samples of malaria (10 in number) and non-malaria patients (31 in number) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). An immunoreactive band was observed at 43 kDa in CSF samples of cerebral malaria patients but not in non-malaria cases when tested with rabbit anti-Plasmodium falciparum antibodies by Western blot analysis. Eleven reactive monoclonal antibodies against P. falciparum were stabilized and expanded. Nine monoclonal antibodies were reactive to CSF samples of cerebral malaria and non-malaria and P. falciparum antigen by dot-ELISA and a common immunoreactive band at 43 kDa by Western blot. One clone Cl-2 was reactive at 43 kDa with CSF of the cerebral malaria patients and also in P. falciparum antigen but at 66 kDa with non-malarial CSF samples in Western blot. The other two clones (Cl-6 and 14) reacted with 3/31 (90% specific) and 8/31 (74%) CSF samples of non-malaria patients, respectively. The monoclonal antibody based ELISA reported in the present study using clone-6 can therefore offer another possibility for developing rapid, easy-to-perform, low-cost tests for diagnosis of cerebral malaria in CSF samples. Western blot using clone-2 might be useful for the detection of cerebral malaria antigen in CSF. [ABSTRACT FROM AUTHOR]

The article describes the case of a 54-year-old man who have urinary tract infection and acute renal failure. He complained of fever and reduced urinary output and altered sensorium. The man developed a sudden onset of lower limb flaccid paralysis 3 days after the second epidural injection of depomedrol for prolapsed intervertebral disk (PIVD). The results of his imaging studies are given including USG abdomen. Treatments given to the patient include intravenous (IV) antibiotics along with central venous pressure (CVP)-guided fluids.

Introduction: The role of pre‐HCT chest high‐resolution computed tomography (HRCT) and serum galactomannan index (GMI) in predicting the post‐allogeneic hematopoietic cell transplant (HCT) invasive pulmonary aspergillosis (IPA) is debatable. Methods: This was a single‐center, prospective study from 2014 to 2019. The primary objective was to study if pre‐HCT chest HRCT and serum GMI predicted IPA post‐HCT. The secondary objective was day +100 mortality. All consecutive, consenting patients of ≥12 years of age undergoing allo‐HCT were included and had pre‐HCT chest HRCT and serum GMI. All patients received mold active antifungal prophylaxis. The EORTC/MSG criteria were used for the diagnosis of IPA. Results: A total of 82 patients with median age 27 years (12‐59 years) were included. The underlying diagnoses included hematological malignancies (79%) and aplastic anemia (21%). Fifteen percent of patients was treated for prior history of probable IPA (>6 weeks before HCT). Pre‐HCT chest HRCT satisfied EORTC clinical criteria in 24% patients. Serum GMI ≥0.5 was seen in 27% of patients. Post‐HCT probable IPA was seen in 24% of patients. There were more patients with pre‐HCT chest HRCT findings satisfying EORTC clinical criteria (45% vs. 18%, P =.014) and GMI ≥0.5 (45% vs. 21%, P =.03) in the group with post‐HCT IPA compared to those without IPA. There was higher day+100 mortality in patients with post‐HCT IPA (55% vs. 18%, P =.001). Conclusions: The presence of EORTC clinical criteria on pre‐HCT chest HRCT, serum GMI ≥0.5, and prior history of IPA predicted post‐HCT IPA. [ABSTRACT FROM AUTHOR]

Renal involvement in 204 cases with multiple myeloma admitted over a 10-year period to this tertiary care center in north India was retrospectively examined. Renal involvement occurred in 55 cases (27%); the vast majority of whom (94.5%) had presented with renal failure and 7.3% had nephrotic syndrome. The diagnosis of multiple myeloma was made after admission in 51 of the 55 (92.7%) cases. Oliguria was seen in 23.6% and two-third patients required dialysis. Factors precipitating renal failure were identified in 53% and included dehydration (33%), hypercalcemia (24%), nephrotoxic drugs (16%), sepsis (9%), recent surgery (5%) and contrast media (2%). Severe anemia, hypercalcemia, Bence Jones proteinuria and skeletal abnormalities were more frequent in those with renal involvement. Patients with renal involvement were more likely to have a high tumor burden. The myeloma was of light chain type in 68% of those with renal involvement whereas IgG myeloma was commonest (57%) in those without evidence of renal disease. Renal histology was studied in 27 cases with myeloma cast nephropathy seen in over 60%. Tubulointerstitial nephritis was seen in 14% cases, 11% had amyloidosis, 7% had acute tubular necrosis and 3.6% each had nodular glomerulosclerosis and plasma cell infiltration. In 8 cases (14.6%), renal biopsy provided the first clue to the diagnosis of myeloma. Renal function improved in 33% cases. Only 22% of patients on dialysis survived over 6 months. Median survival in those with renal involvement was only 4 months. Development of unexplained renal failure in an elderly individual with normal sized kidneys, in association with disproportionate anemia even in the absence of skeletal lesions should alert the physician to the diagnosis of multiple myeloma. [ABSTRACT FROM AUTHOR]

Lenalidomide maintenance after frontline chemo-immunotherapy (CIT) in chronic lymphocytic leukemia (CLL) has not been standard due to the availability of novel therapies, though these remain out of reach for most in low-middle income countries. This single-center, open-label study randomized CLL patients (non-deletion 17p) after frontline therapy to lenalidomide maintenance (dose-escalated 2.5–10mg, 20/28 days per cycle for six months) or observation (2:1 allocation). Forty patients were included over 2018–2020. At a median follow-up of 22 months, median progression-free survival (PFS) with lenalidomide was not significantly different than observation (26 vs. 18 months, p = 0.4). Patients with minimal residual disease >10−2 had a trend toward better PFS with lenalidomide (19 vs. 7 months, p = 0.07). Grade 3 neutropenia was seen in 16.7% of patients on lenalidomide. Quality of life was comparable between the two arms. Low dose, fixed duration lenalidomide maintenance is not an effective strategy after frontline CIT in CLL. [ABSTRACT FROM AUTHOR]

Acute Promyelocytic Leukemia (APL) is associated with excellent long-term outcomes. However, early mortality due to coagulopathy remains a challenge. In this study we examined the bleeding and thrombotic manifestations, as well as incidence of Early Death secondary to thrombosis/hemorrhage (ED-TH) in patients with APL. Early death (ED) was defined as death occurring within 30 days of induction therapy. Two-hundred forty-eight patients were included in the study. Overall, 57 patients had evidence of a major bleed/thrombosis at presentation or during induction therapy, including 44 patients with a major bleed, 8 patients with thrombosis and 5 patients with both evidence of thrombosis and a major bleed. Forty patients (16.1%) had ED, of which 21 had ED-TH. The cumulative incidence of death due to thrombo-hemorrhagic complications at 30 days was 8.4%. On univariate analysis, increasing Prothrombin time (PT)(p-<0.001), white blood cell count (p < 0.001) and activated Partial thromboplastin time (aPTT) (p < 0.001) were statistically significantly associated with increased risk of ED-TH. However, on multivariate analysis, only increasing PT (p-0.025) and aPTT (p-0.041) were significantly associated with increased risk of ED-TH. • Bleeding/Thrombosis is majorly responsible for early death in Acute Promyelocytic Leukemia (APL). • Factors associated with early death due to bleed/thrombosis (ED) in APL patients were analysed. • Prothrombin Time and activated partial thromboplastin time were associated with increased risk of ED. • Better predictors of ED may help improve outcomes further in patients with APL. [ABSTRACT FROM AUTHOR]

Background: A number of mutations have been reported to occur in patients with acute myeloid leukemia (AML), of which NPM1 and FLT3 genes mutations are the commonest and have important diagnostic and therapeutic implications. Material and Methods: Molecular testing for NPM1 and FLT3 genes was performed in 92 de-novo AML patients. The frequency and characteristics of NPM1 and FLT3 mutations were analyzed. Results: Nucleophosmin 1(NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutations were seen in 22.8% and 16.3% of patients, respectively. Amongst FLT3 mutations, FLT3-ITD mutation was seen in 8.7% cases, FLT3-TKD in 5.4%, and FLT3-ITD+TKD in 2.2% cases. Certain associations between the gene mutations and clinical characteristics were found, including in NPM1 mutated group-female preponderance, higher incidence in M4/M5 categories and decreased expression of CD34 and HLA-DR; and in FLT3-ITD mutated group-higher age of presentation, higher total leucocyte count and blast percentage. Conclusion-AML patients with NPM1 and FLT3 mutations have differences in clinical and hematological features, which might represent their different molecular mechanism in leukemogenesis. The frequency of NPM1 and FLT3 mutations in this study was comparable to reports from Asian countries but lower than that reported from western countries. However, as the number of patients in the study was less, a larger number of patients need to be studied to corroborate these findings. [ABSTRACT FROM AUTHOR]

Introduction: The quality of life (QoL) analysis is likely to differ by region, ethnicity, and questionnaires in comparison with age‐matched healthy controls. Methods: The EORTC QLQ‐C30 and QLQ‐CLL17 questionnaire validated in regional languages were administered to 127 consecutive CLL and 100 age‐matched, healthy controls at a single center from 2018 to 2019. Results: All groups of CLL patients either on wait and watch (W&W) or on treatment had significantly impaired QoL in all functional domains including global health compared to controls (P <.0001). CLL patients had significantly higher symptom scores than controls in most domains (P <.0001, 0.03 for diarrhea). There was no difference in the QoL by age or gender. Lower socioeconomic status patients had higher financial difficulty (P =.02). Patients on CIT had the worst global health (OR 12.21 compared to patients on W&W) (P =.03). Patients on ibrutinib had less worries/fears about health and functioning than patients who were on CIT (P =.04). Conclusions: Quality of life is severely affected in CLL patients on W&W. Global health status and worries about future health and functioning were major concerns. Socioeconomic status but not age or gender impacted QoL. Patients on ibrutinib had better QoL than on CIT. [ABSTRACT FROM AUTHOR]

Post Graduate Institute (PGI) Chandigarh is a premier institute of North India. There are approximately 70,000 admissions per year. The adult clinical hematology department sees more than 2000 new patients per year. A preliminary analysis of 299 chronic myeloid leukemia patients registered from January 2001 until December 2007 was done. Out of these, 256 (86%) patients were in chronic phase (CP). The median age at presentation was 40 years. At 6 months of follow-up 95% of patients who were started on Imatinib mesylate based therapy remained in CP. Partial cytogenetic remission was seen in 69% of patients while complete cytogenetic response was seen in only 20% of patients at 6 months on Imatinib mesylate. [ABSTRACT FROM AUTHOR]

The need for prognostication in chronic lymphocytic leukemia (CLL) is felt due to the heterogeneous clinical course of CLL, to counsel the patients, tailor follow-up, and to guide treatment decisions. There were predominantly CLL patients on wait and watch in our cohort compared to patients in the CLL-IPI cohort (48% I vs. i 19%, I p i <.0001). The CLL-IPI incorporating comprehensive patient data from prospective clinical trials were proposed in 2016 by a group of international CLL experts to be the standard of care in reporting of clinical trials and clinical practice. [Extracted from the article]

Summary: Mesenchymal stromal cells (MSCs) demonstrate the properties of self‐renewal, multipotentiality, and immunosuppression, which are responsible for their widespread clinical applications in tissue repair and regeneration. MSCs have been isolated from bone marrow, adipose tissue, and cord blood using culture in specialised media. Their presence in peripheral blood (PB) is debatable. We studied the presence of MSCs at baseline (PB) and following mobilisation with growth factors [PB and apheresis product (AP)] in patients undergoing autologous stem cell transplantation and healthy donors using flow cytometry. We conclude that both mobilised PB and AP are potential sources of MSCs. Given their small numbers in PB/AP, clinical use is feasible following ex‐vivo expansion. Variables affecting the presence of MSCs in PB and AP are also discussed. [ABSTRACT FROM AUTHOR]

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p < 0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php. [ABSTRACT FROM AUTHOR]

Background: Aberrant phenotypes in acute leukemia have been reported with varying frequencies in independent studies and their association with prognostic factors is still a matter of debate.Aim: This study aims to identify the frequency of aberrant immunophenotypes in de novo acute myeloid leukemia (AML) and to evaluate their association with initial clinical and hematological features.Materials and Methods: A total of 181 patients of de novo AML were included during the time (July 2010-June 2012). The immunophenotype of all cases of AML was studied by using flow cytometry.Results: Aberrant lymphoid antigen expression was seen in 43.1% cases. Most frequent aberrant lymphoid antigen was CD7, seen in 26.5% cases. All French-American-British (FAB) subtypes except AML-M3 expressed aberrant lymphoid antigens. The expression was most common in AML-M4 in the current study. CD34 expression in AMLs was significantly associated with the expression of aberrant lymphoid antigens. Lymphoid antigen expression in adult AML was significantly associated with higher white blood cell (WBC) count (>50,000/mm3) and higher number of peripheral blasts (>70%).Conclusion: In summary, CD7 is the most common aberrant lymphoid antigen expressed in AML. FAB subtype AML-M3 is usually not associated with aberrant lymphoid antigen expression. AML cases with CD34 positivity are more likely to express aberrant lymphoid markers. The current study also supports that aberrant lymphoid antigen expression in adult AML is associated with adverse presenting hematological features (WBC count >50,000/mm3, peripheral blasts >70%). Pediatric Ly + AML cases are not associated with adverse presenting clinical and biological features. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the spectrum of genetic defects in Indian patients with unexplained erythrocytosis. Methods: Fifteen families (18 patients) with unexplained erythrocytosis were enrolled after excluding polycythemia vera and secondary erythrocytosis. Focused Sanger sequencing from genomic DNA was performed for EPOR (exon 8), VHL (exons 2‐3), EGLN1 (exons 2‐5), EPAS1 (exon 12), and all exons of HBB, HBA1, and HBA2 genes. Results: Eleven of the 18 patients (including two pairs of brothers) had Chuvash polycythemia, that is, homozygosity for VHL:c.598C > T (p.Arg200Trp). Three patients (two of whom were brothers) had HBB mutations associated with increased oxygen‐affinity hemoglobin—one had a heterozygous Hb McKees Rocks HBB:c.438T > A (p.Tyr146*), and two brothers showed heterozygous Hb Rainier HBB:c.437A > G (p.Tyr146Cys). No pathogenic variants were found in the remaining four cases. Conclusion: A gene‐by‐gene Sanger sequencing approach could determine a genetic basis for erythrocytosis in 11 of the 15 (73%) Indian families, with homozygous VHL:c.598C > T (p.Arg200Trp) being the commonest pathogenic variant. This first study from the Indian subcontinent provides a rationale for analyzing this variant in patients with suspected congenital erythrocytosis from this region. Rare first occurrences of Hb McKees Rocks and Hb Rainier in Indians are also being reported. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Pregnancy: part of life in chronic myelogenous leukemia," by A. D. Law, D. Kim, J. H. Lipton in the 2016 issue.

Background: Geriatric anemia is a global health problem because of its high prevalence and associated significant morbidity and mortality. Aim: The objectives of this study were to estimate the pattern of anemia in the elderly patients and the underlying etiology of anemia. Research Design and Methods: This was a hospital-based prospective observational study, conducted in patients aged 60 years and above at PGIMER, Chandigarh, a tertiary care center of North India. Anemia is defined as hemoglobin level less than 13 g/dl in men and 12 g/dl in women. Results: Among the 105 older patients with anemia, the mean value of hemoglobin was 8.8 ± 2.3 g/dl. The etiological distribution of anemia was iron deficiency in 26 patients (24.8%), chronic disease in 24 patients (22.9%), hematological disorders in 21 (20%), chronic kidney disease in 13 (12.4%), multifactorial in 8 (7.6%), vitamin B12 deficiency in 2 (1.9%), folate deficiency in 1 (0.9%), and hypothyroidism in 1 patient (0.9%). No etiology could be found in 9 patients (8.6%). 57.6% of the iron-deficient patients had upper gastrointestinal lesions and 30.7% had a nutritional cause. Common chronic diseases causing anemia were malignancy (36.6%) and liver disease (29.1%). The myelodysplastic syndrome was the commonest hematological disorder. 53.35% of the patients had normocytic anemia, 40% had microcytic anemia, and 6.6% had macrocytic anemia. Conclusions: In most of the cases, anemia in the elderly had a treatable cause. Thus, a thorough investigation including gastrointestinal endoscopy is warranted. Unexplained progressive or unresponsive anemia requires bone marrow examination. [ABSTRACT FROM AUTHOR]

The data on adolescent and young adult chronic myeloid leukemia (AYA-CML) from the Indian subcontinent are scarce. We studied characteristics of AYA-CML through a retrospective analysis of 1950 CML patients registered to a tertiary care hospital in Northern India. AYA-CML represented 22.1% of all CML patients, with cumulative overall survival (OS) of 84%, and 1 and 8 years OS of 94.2% and 74.2%, respectively. Of all cases, 8.91% patients had advanced disease at the time of diagnosis, and 13.95% had myelofibrosis in the diagnostic marrow, 79.6% had complete cytogenetic response (CCyR), and 84.5% had major molecular response (MMR). Loss of CCyR and MMR was noted in 37.2% and 28.4%, respectively. The cumulative OS was significantly better in patients on patient assistance program, and they were initiated on therapy within 3 months of symptom onset. [ABSTRACT FROM AUTHOR]

Summary: The pivotal role of erythropoietin (EPO) in hypoxic adaptation has led to various studies assessing the EPO and ferritin response in native highlanders from Andes and Tibet. We assessed the relationship between EPO, haemoglobin and ferritin in 335 native highlanders (172 boys and 163 girls, aged 4 to 19 years) from Leh‐Ladakh, India, who had no history of travel to lowland areas. Complete blood counts, serum EPO and ferritin levels were measured. We stratified study subjects based on age, gender, pubertal status and analysed the EPO and ferritin levels between the stratified groups respectively. The mean EPO level in boys was lower than girls. The mean ferritin level in boys was significantly higher (P = 0·013) than in girls. There was no significant variation in the EPO and ferritin levels amongst the various age groups in our study. Near normal EPO levels since childhood with a negative correlation with haemoglobin is suggestive of a robust adaptive mechanism to high altitude from the early years of life. Low ferritin levels are indicative of decreased iron stores in these native highlanders. [ABSTRACT FROM AUTHOR]