-
[show abstract]
[hide abstract]
ABSTRACT: Background & objectives: Busulfan (Bu) in combination with cyclophosphamide is widely used in myeloablative conditioning regimen prior to haematopoietic stem cell transplantation (HSCT). Its narrow therapeutic range and toxic side effects at high systemic exposure and graft rejection at low exposure emphasize the need for busulfan dose optimization using targeted dose adjustment prior to HSCT. We report here a rapid and sensitive method to quantitate busulfan plasma levels in patients receiving busulfan as part of pre-transplant conditioning. Methods: The method involves simple protein precipitation of the plasma followed by analysis using a high performance liquid chromatography (HPLC) with tandem mass spectrometry - electrospray ionization technique (LC-ESI MS/MS) in positive ionization mode and quantified using multiple reaction monitoring (MRM). Deuterated busulfan (d 8 -busulf`an) was used as the internal standard. Results: The method was linear for the concentration ranging from 0 to 4000 ng/ml of busulfan with a limit of detection of 2 ng/ml and limit of quantitation of 5 ng/ml. The assay was accurate for serial concentrations of Bu in plasma for five consecutive days and the CV was less than 10 per cent. Conclusion: Using this rapid and sensitive method, busulfan levels were targeted and subsequent doses adjusted at our center in 26 patients receiving high dose busulfan in combination with cyclophosphamide or fludarabine.
The Indian journal of medical research 04/2013; 137(4):777-784. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND AND AIM: Over the last few decades, epidemiologic studies from the West have shown changing trends in etiology and clinical outcomes in patients with nonvariceal upper gastrointestinal bleed (NVUGIB). There are limited data from India on the current status of NVUGIB. The aim of this study therefore was to assess the etiological profile and outcomes of patients with NVUGIB at our center. METHODS: We prospectively studied all patients (≥15 years) who presented with NVUGIB over a period of 1 year. The clinical and laboratory data, details of endoscopy, and course in hospital were systematically recorded. Outcome measures assessed were rebleeding rate, surgery, and mortality. RESULTS: Two hundred and fourteen patients (age, ≥15 years) presented to us with NVUGIB during the study period. The mean age was 49.9 ± 16.8 years and 73.8 % were males. Peptic ulcer was the commonest cause (32.2 %) of NVUGIB. About one third of patients required endoscopic therapy. Rebleeding occurred in 8.9 % patients, surgery was required in 3.7 %, and mortality rate was 5.1 %. Rebleeding and mortality were significantly higher among inpatients developing acute NVUGIB compared to those presenting directly to the emergency room. CONCLUSIONS: Peptic ulcer was the most common cause of NVUGIB. Outcomes (rebleed, surgery, and mortality) at our center appear similar to those currently being reported from the West.
Indian Journal of Gastroenterology 03/2013;
-
[show abstract]
[hide abstract]
ABSTRACT: Improving clinical outcomes among high risk Class III β thalassemia major patients (Class IIIHR) receiving an allogeneic SCT remains a challenge. From October, 2009 a treosulfan based regimen (TreoFluT) was used for all consecutive Class III patients (n = 50). The clinical outcomes were compared with the historical conventional busulfan (BuCy) based regimen (n = 139). Use of TreoFluT was associated with a significantly reduced incidence of sinusoidal obstruction syndrome (SOS) among Class IIIHR cases (78% to 30%; P = 0.000) and early TRM (46% to 13%; p = 0.005). There was also a trend towards better engraftment in the Class IIIHR subset (P = 0.055). However, the use of bone marrow (BM) as source of stem cells along with the TreoFluT regimen was associated with 50% early mixed chimerism which reduced to 8.5% with the use of a peripheral blood stem cell graft (PBSC). Use of a PBSC graft was not associated with a significant increase in the incidence of acute or chronic graft versus host disease (GVHD). The overall and event free survival was significantly better among the Class IIIHR subset with the use of TreoFluT Vs. BuCy (86.6±7.3 Vs. 39.4±6.8%; P = 0.002 and 77.8±8.8 Vs. 32.4±6.5%; P = 0.003 respectively). A TreoFluT conditioning regimen with a PBSC graft can significantly improve clinical outcomes of Class IIIHR patients.
PLoS ONE 01/2013; 8(4):e61637. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background : Chronic myelogenous leukemia (CML) is characterised by the t(9;22)(q34;q11.2) which results in the formation of the BCR/ABL1 fusion gene. Occasionally, the t(9;22) may be associated with submicroscopic deletions of chromosomes 9 and/or 22 which appear to be associated with a worse prognosis. Three or four-way variant t(9;22) may also occur. All these changes as well as gain of the Philadelphia chromosome which represents disease progression can be detected by fluorescence in situ hybridization (FISH) analysis. FISH analysis at presentation is used to determine the number of cells with BCR/ABL1 fusion and establish whether the patterns are typical or atypical. Response to therapy can then be monitored by serial testing. Patients and Methods : The study group consisted of all patients diagnosed or suspected to have CML who had interphase FISH analysis at presentation on peripheral blood/bone marrow using a commercially available BCR/ABL1 dual colour, dual fusion probe. The study was performed at a tertiary hospital in India between 2004 and 2010. Results: There were 1076 diagnostic samples which were positive for BCR/ABL1 fusion. Typical dual fusion signals (two fusions, one red and one green, 2F1R1G) were seen in 801 cases (74 %). Atypical signal patterns were seen in 275 cases (26%). These were: 1F1R2G (4%), 1F2R1G (2.5%) and 1F1R1G (11%) representing deletions of the derivative 9 involving chromosome 9 sequences, chromosome 22 sequences, or both respectively; 3F1R1G (6.5%) usually representing gain of an additional Philadelphia chromosome and 1F2R2G (1%) representing a three- or four-way variant translocation. More than one signal pattern was seen in 1%. Conclusions: Our findings were similar to the literature with respect to the distribution of signal patterns except that we had a lower number of patients with variant translocations. While each signal pattern is typically associated with a particular abnormality, there can be more than one explanation for each pattern. Hence, metaphase FISH analysis is the "gold standard" for the interpretation of signal patterns.
Indian Journal of Pathology and Microbiology 07/2012; 55(3):347-51. · 0.68 Impact Factor
-
Sachin David,
Giridhara Rao Jayandharan,
Aby Abraham,
Rintu R Jacob,
Govindanattar Sankari Devi,
Nikhil Patkar,
Ramachandran V Shaji,
Sukesh C Nair,
Auro Viswabandya,
Rayaz Ahmed, Biju George,
Vikram Mathews,
Mammen Chandy,
Alok Srivastava
[show abstract]
[hide abstract]
ABSTRACT: Wiskott-Aldrich syndrome (WAS) [OMIM: 301000] is an X-linked immunodeficiency disease characterized by thrombocytopenia and small platelets, eczema, recurrent infections, with an increased risk for autoimmunity and malignancy (1, 2). The gene responsible for this syndrome, WAS, comprises 12 exons and approximately 1.8kb in length (3). WAS encodes a 502-amino acid protein (WASp) that is expressed selectively in haematopoietic stem cell-derived lineages and is involved in cell signaling and cytoskeleton reorganization(4).A milder allelic variant caused by WAS gene mutation leads to X-linked thrombocytopenia (XLT), a congenital disorder characterized by thrombocytopenia and small platelets but, in general, without the other complications of WAS (5). © 2012 John Wiley & Sons A/S.
European Journal Of Haematology 06/2012; 89(4):356-60. · 2.61 Impact Factor
-
Savitha Varatharajan,
Ajay Abraham,
Wei Zhang,
R V Shaji,
Rayaz Ahmed,
Aby Abraham, Biju George,
Alok Srivastava,
Mammen Chandy,
Vikram Mathews,
Poonkuzhali Balasubramanian
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: The present study aimed to investigate the role of expression of daunorubicin-metabolizing enzymes carbonyl reductase 1 and 3 (CBR1 and CBR3) on the in vitro cytotoxicity of daunorubicin in primary acute myeloid leukemia (AML) cells and the effect of genetic variants in CBR1 and CBR3 on the plasma pharmacokinetics of daunorubicin and daunorubicinol (DOL) in AML patients. METHODS: RNA expression of CBR1 and CBR3, intracellular daunorubicin and DOL levels, and in vitro cytotoxicity of daunorubicin were measured in bone marrow mononuclear cells of 104 adult AML patients. Plasma pharmacokinetics of daunorubicin and DOL was measured in 24 patients receiving daunorubicin-based induction chemotherapy for AML. RESULTS: Increased expression of CBR1 significantly reduced the in vitro cytotoxicity of daunorubicin and also positively correlated with intracellular DOL levels. Polymorphisms in CBR1 and CBR3 did not show any association with intracellular daunorubicin or DOL levels, but there was a trend towards significant increase in plasma daunorubicin systemic exposure in patients with a variant genotype for CBR1 polymorphism rs25678. CONCLUSIONS: This pilot study suggests that CBR1 RNA expression may be helpful in identifying AML patients at risk of developing resistance or toxicity to daunorubicin due to increased formation of DOL. Further confirmation of these findings in a larger sample pool would be required to determine the applicability of these results. Inhibition of CBR1 can be an option to improve the efficacy and prevent toxicity related to the treatment. Influence of daunorubicin and DOL plasma levels on clinical outcome, if any, remains to be evaluated.
European Journal of Clinical Pharmacology 05/2012; · 2.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In addition to standard risk criteria at diagnosis, minimal residual disease (MRD) following initiation of therapy is a well-recognized risk factor to predict relapse. Literature from developing countries addressing therapeutic or laboratory practices related to MRD, is largely lacking. In a first paper from India, we describe our experience in establishing a flow cytometry-based MRD assay for precursor B lineage ALL (BCP-ALL) with emphasis on the assay standardization and cost.
Normal templates for B cell development were established in 10 control patients using CD45, CD11a, CD38, CD20, CD10, CD19, CD58, CD34, CD123, and CD22. BCP-ALL samples (n = 42) were characterized at diagnosis to identify a suitable marker for follow-up during mid (D+21) and end of induction (D+33). Both, multiparametric immunophenotyping and single marker detection of LAIP were used for data analysis.
In 95.2% of BCP-ALL at least two informative markers could be obtained when a minimum of four cocktail combinations were used. The combination CD20, CD10, CD45, and CD19 was the most useful (71.4%) followed by combinations containing CD38 (66.7%), CD22 (57.1%), CD11a (52.4%), and CD58 (33.3%). Using our approach, 60 and 47% of patients had detectable MRD at mid and end induction time points, respectively.
We have described a relatively cost effective MRD panel which is applicable to over 90% of patients. We hope that this data would encourage more centers in India and other resource constrained health delivery systems to develop MRD assays.
Cytometry Part B Clinical Cytometry 03/2012; 82(4):252-8. · 2.53 Impact Factor
-
Minoo Battiwalla,
Kristin Ellis,
Peigang Li,
Steven Z Pavletic,
Gorgun Akpek,
Peiman Hematti,
Thomas R Klumpp,
Richard T Maziarz,
Bipin N Savani,
Mahmoud D Aljurf, [......],
Theresa Hahn,
Nandita Khera,
Mark R Litzow,
Alison W Loren,
Wael Saber,
Mukta Arora,
Alvaro Urbano-Ispizua,
Corey Cutler,
Mary E D Flowers,
Stephen R Spellman
[show abstract]
[hide abstract]
ABSTRACT: The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2012; 18(8):1302-8. · 3.15 Impact Factor
-
Minoo Battiwalla,
Tao Wang,
Jeanette Carreras,
H Joachim Deeg,
Mouhab Ayas,
Rajinder P S Bajwa, Biju George,
Vikas Gupta,
Ricardo Pasquini,
Hubert Schrezenmeier,
Jakob R Passweg,
Kirk R Schultz,
Mary Eapen
[show abstract]
[hide abstract]
ABSTRACT: The HLA class II DRB1 antigen DR15 (common alleles *1501, *1502) is an important marker in the pathobiology of severe aplastic anemia (SAA). We studied 1204 recipients of HLA-matched sibling bone marrow transplantation for SAA to determine whether HLA DR15 status (as determined by allele-level typing) affected hematopoietic recovery, graft-versus-host disease (GVHD), or overall survival (OS). In multivariate analysis, secondary graft failure rate at 2 years was lower in patients who were HLA DR15+ (hazard ratio = 0.46, P = .01). However, neutrophil recovery at day -28, platelet recovery at day -100, acute GVHD, chronic GVHD, and overall mortality were independent of DR15 status. The 5-year probabilities of OS, after adjusting for age, race, performance score, transplant-conditioning regimen, and year of transplantation, were 78% and 81% for patients who were HLA DR15+ and HLA DR15-, respectively (P = .35). In conclusion, DR15 status is associated with secondary graft failure after HLA-matched sibling bone marrow transplantation for SAA but has no significant impact on survival.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2012; 18(9):1401-6. · 3.15 Impact Factor
-
Ezhilarasi Chendamarai,
Poonkuzhali Balasubramanian, Biju George,
Auro Viswabandya,
Aby Abraham,
Rayaz Ahmed,
Ansu Abu Alex,
Saravanan Ganesan,
Kavitha M Lakshmi,
Usha Sitaram,
Sukesh Chandran Nair,
Mammen Chandy,
Nancy Beryl Janet,
Vivi M Srivastava,
Alok Srivastava,
Vikram Mathews
[show abstract]
[hide abstract]
ABSTRACT: Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.
Blood 02/2012; 119(15):3413-9. · 9.90 Impact Factor
-
Ajay Abraham,
Savitha Varatharajan,
Salar Abbas,
Wei Zhang,
Ramachandran V Shaji,
Rayaz Ahmed,
Aby Abraham, Biju George,
Alok Srivastava,
Mammen Chandy,
Vikram Mathews,
Poonkuzhali Balasubramanian
[show abstract]
[hide abstract]
ABSTRACT: Cytidine deaminase (CDA) irreversibly deaminates cytarabine (Ara-C), a key component of acute myeloid leukemia (AML) induction and consolidation therapy. CDA overexpression results in Ara-C resistance, while decreased expression is associated with toxicity. We evaluated factors influencing variation in CDA mRNA expression in adult AML patients and normal controls, and how they contributed to Ara-C cytotoxicity in AML cells.
CDA mRNA expression in 100 de novo AML patients and 36 normal controls were determined using quantitative reverse-transcriptase PCR. Genetic variants in the CDA gene were screened by direct sequencing. IC₅₀ of Ara-C was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
CDA RNA expression as well as Ara-C IC₅₀ showed wide variation in AML samples and normal controls. Fourteen sequence variants were identified, three of which (-33delC, intron 2 TCAT repeat and the 3´untranslated region 816delC variants) showed significant association with RNA expression and the nonsynonymous coding variant 79A>C was associated with Ara-C cytotoxicity.
CDA genetic variants explain the variation in RNA expression and may be candidates for individualizing Ara-C therapy.
Pharmacogenomics 02/2012; 13(3):269-82. · 3.97 Impact Factor
-
Shanmugaapriya Sellathamby,
Kavitha M Lakshmi,
Marc Busson,
Auro Viswabandya, Biju George,
Vikram Mathews,
Mammen Chandy,
Dominique Charron,
Rajagopal Krishnamoorthy,
Ryad Tamouza,
Alok Srivastava
[show abstract]
[hide abstract]
ABSTRACT: In this study, the impact of polymorphisms in the genes of proinflammatory (IL-β, TNF-α, IL-6, IFN-γ), anti-inflammatory (transforming growth factor [TGF]-β, IL-10, IL-Ra), and other immunoregulatory factors (FcγRIIa, NOS3) along with the conventional risk factors on the rate of hematopoietic recovery and first episodes of bacterial, viral, or invasive fungal infections in 102 patients with β-thalassaemia major who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with relatively uniform protocols at our center from June 1995 to June 2004 with a minimum follow-up of at least 2 years were studied retrospectively for 180 days after hematopoietic stem cell transplantation (HSCT). Our data show that (1) donor IL-1RN∗2/2 (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.17-5.09; P = .018) and FCγRIIA +4481G/G genotypes (HR, 3.1; 95% CI, 1.56-6.31; P = .001) increased the incidence of bacterial infection; (2) fungal infection was increased in recipients with whose donors had IFN-γ +874T/T genotype (HR, 3.8; 95% CI, 1.08-13.62; P = .037); (3) time to neutrophil recovery was shorter in splenectomized patients (HR, 3.1; 95% CI, 1.70-5.64; P < .001), donors without IL-10 -1082A, -819T, and -592A haplotype (HR, 1.6; 95% CI, 1.02-2.39; P = .039), and recipients with IFN-γ +874A/A genotype (HR, 1.6; 95% CI, 1.05-2.56; P = .029); and (4) time to platelet recovery was shorter in patients with IL-10 -1082A/A genotype (HR, 1.8; 95% CI, 1.14-2.68; P = .010) and with donors having TNF-α -308G/G genotypes (HR, 1.8; 95% CI, 1.06-2.93; P = .028). These data suggest that outcome after allogeneic stem cell transplantation could be affected by many factors. The mechanisms by which they bring about such impact needs further evaluation.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2012; 18(8):1219-26. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Achieving a major molecular response (MMR) is an important predictor of progression-free survival in chronic myeloid leukemia patients treated with imatinib. This requires accurate measurement of BCR-ABL1 transcripts normalized to a control gene, as well as defining a level (BCR-ABL1/control gene ratio) that will correlate with sustained clinical response. To make these measurements comparable between laboratories, an international scale (IS) is necessary. A BCR-ABL1/control gene ratio of 0.10% represents MMR in the IS. In collaboration with an international reference laboratory in Adelaide, S.A., Australia, we have established and validated a lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS. In this report, we explain the process and steps involved in obtaining a valid lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS.
Acta Haematologica 01/2012; 127(3):135-42. · 1.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mammalian excision repair cross-complementing 1 (ERCC1) and ERCC4 (a.k.a xeroderma pigmentosum complementation group F) are nucleotide excision repair enzymes, which excise the 5' end of damaged DNA. ERCC1 and ERCC4 have an interactive relationship with poly (adenosine diphosphate ribose) polymerase (PARP). We studied the role of ERCC1 and ERCC4 in glucose-induced extracellular matrix protein production in human endothelial cells and in the retinas and kidneys of streptozotocin diabetic rats.
Human umbilical vein endothelial cells were grown with low (5 mM) and high glucose (25 mM). The cells were subjected to ERCC1 and ERCC4 small interfering RNA transfections, PARP blocker (3-aminobenzamide, ABA) and p300 blocker (curcumin). Retinas and kidneys from 1-month-old streptozotocin diabetic rats with or without treatment with curcumin and ABA were examined. Cells and tissues were studied for oxidative stress markers, fibronectin, ERCC1 and ERCC4, PARP and p300 mRNA. Western blot of nuclear proteins was performed.
ERCC1 and ERCC4 messenger RNA and protein levels were higher in high glucose than in low glucose, along with increasing oxidative stress and augmented p300 and fibronectin production. ABA, curcumin, ERCC1 and ERCC4 silencing reduced such upregulations and oxidative stress. Similar changes were seen in the kidneys and retinas of diabetic rats. ABA and curcumin treatment significantly reduced such changes.
These data indicate that glucose-induced ERCC1 and ERCC4 upregulation leads to increased fibronectin production via a p300-dependent pathway in umbilical endothelial cells, as well as in the retina and in the kidneys of streptozotocin diabetic rats. ERCC1 and ERCC4 may play important roles in the development of diabetic retinopathy and nephropathy.
Diabetes/Metabolism Research and Reviews 01/2012; 28(4):329-37. · 3.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Molecular characterization of β-thalassemia (β-thal) is essential in prevention and in understanding the biology of the disease. Deletion mutations are relatively uncommon in β-thal. In this report, we describe a novel 26 bp deletion from codon 6 to codon 14 in the β-globin in a consanguineous family from Tamil Nadu, India. This novel mutation causes a shift in the normal reading frame of the β-globin coding sequence, and consequently, a premature chain termination of translation due to the creation of a stop codon at the position of codon 21. The identification of this novel deletional mutation adds to the repertoire of β-thal mutations in India.
Hemoglobin 01/2012; 36(1):98-102. · 1.30 Impact Factor
-
Nikhil Patkar,
Sheila Nair,
Ansu Abu Alex,
Mayur Parihar,
Marie Therese Manipadam,
Neeraj Arora,
Rayaz Ahmed,
Aby Abraham, Biju George,
Auro Viswabandya,
Vivi Srivastava,
Alok Srivastava,
Vikram Mathews
[show abstract]
[hide abstract]
ABSTRACT: In a first series from India, we report 9 cases of hepatosplenic T cell lymphoma (HSTCL) seen in 23 months accounting for 4.2% of all mature T-non-Hodgkin lymphomas (NHLs) in our institution. All patients presented with organomegaly, cytopenias and had evidence of bone marrow involvement. The tumor cells had a blastic (55%) morphology with predominantly intrasinusoidal (33.3%) or intrasinusoidal with an additional interstitial component (33.3%). On flow cytometry, the classical phenotype (CD3+, CD7+, CD4-, CD8-, CD5-, CD56+/-) was seen only in 4 patients. Unusual variations included CD45 (overexpression), CD7 (dim expression), CD3 (overexpression, heterogeneous and dim), CD2 (overexpression), CD5 (heterogeneous), CD8 (heterogeneous or dim or overexpression) and aberrant expression of CD19. Fluoresvent in situ hybridisation (FISH) and karyotyping was abnormal in 5 out of 7 patients evaluated. All of the 5 cases showed abnormalities in chromosome 7 (ring chromosome or isochromosome 7q). Five patients died of disease and related complications in a span of 1-3 months after diagnosis whereas 4 were alive at their last follow up out of which 2 had documented a relapse. In our series, HSTCL was characterized by typical clinical and variable immunophenotypic features and a dismal clinical outcome.
Leukemia & lymphoma 09/2011; 53(4):609-15. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The t(8;21)(q22;q22) is the most common translocation in acute myeloid leukemia (AML). We describe the clinicopathologic and cytogenetic profile of 117 patients with t(8;21) AML. There were 76 males and 88 adults. The median age was 26 years. Most patients (80%) had AML M2. Dysplasia was present in 68% of patients and eosinophilia in 18%. Eight patients had fewer than 20% blasts. Additional chromosomal aberrations were seen in 103 patients (88%) with loss of a sex chromosome (LSC) in 78 patients (66%) and deletion 9q in 21 (18%). The other recurrent abnormalities were trisomies 4, 8 and 15, monosomy 17 and deletion 7q (less than 5% each). Three- or four-way variant t(8;21) were seen in 6% of patients and 3% had tetraploidy. Aberrant expression of CD19 was seen in 54% of patients. FLT3 mutations were seen in 7.5% of patients (3/40) and c-KIT mutations in 6.6% (2/30). None had NPM1 or JAK2 V617F mutations. One patient had a granulocytic sarcoma. Complete remission was achieved in 96% of the 26 newly diagnosed patients after first induction. The median follow-up was 25 months (range 4-68). The overall survival was 69% at 31 months.
Leukemia & lymphoma 07/2011; 53(1):103-9. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables.
Thirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated.
In patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D.
Pancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC.
Endocrine Practice 07/2011; 17(6):897-905. · 2.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It is well recognized that arsenic trioxide (ATO) is an efficacious agent for the treatment of acute promyelocytic leukemia (APL). Use of single agent ATO in the treatment of APL leads to remissions which are durable in the majority. ATO is probably the most effective single agent in the treatment of APL and there have been very few reports of primary resistance. It has been used both as a single agent and in combination with other conventional drugs to treat APL. Use of ATO is the accepted standard of care in the management of relapsed APL, where it is often used effectively as a bridge to a stem cell transplant. However, its role in newly diagnosed APL remains controversial. ATO probably has multiple mechanisms of action. Better understanding of its mechanisms of action/s is likely to lead to more rationale use of this agent or its derivatives either alone or in combination with other drugs. There is limited data on the kinetics of leukemia clearance and normal haematopoietic recovery after the administration of single agent ATO for the treatment of APL, preliminary data suggests that it is likely to be different from conventional therapy. There have been a number of concerns of the potential short and long term toxicity of this agent. Most such concerns arise from the toxicity profile noted in people exposed to long term arsenic exposure in the environment. With the therapeutic doses and schedules of administration of ATO in the treatment of malignancies the overall toxicity profile has been favorable. In a resource constrained environments the use of a single agent ATO based regimen is a realistic and acceptable option to treat almost all patients. In the developed world it has the potential in combination with other agents to improve the clinical outcome with reduction of dose intensity of chemotherapy and remains an option for patients who would not tolerate conventional therapy. In this review we focus on the use of single agent ATO for the treatment of APL and summarize our experience and review the literature.
Mediterranean Journal of Hematology and Infectious Diseases 01/2011; 3(1):e2011056.
-
Monika Gupta,
J Ashok Kumar,
Usha Sitaram,
S Neeraj,
A Nancy,
Poonkuzhali Balasubramanian,
Aby Abraham,
Vikram Mathews,
Auro Viswabandya, Biju George,
Mammen Chandy,
Alok Srivastava,
Vivi M Srivastava
[show abstract]
[hide abstract]
ABSTRACT: Among patients with acute myeloid leukemia (AML), the t(6;9) (p22;q34) is a rare but defined subset with a poor prognosis. We report 16 patients with the t(6;9), of whom 13 had AML, 2 had myelodysplastic syndrome (MDS), and 1 had chronic myeloid leukemia in myeloid blast crisis (CML-BC). All except for one were evaluated at diagnosis. The median age was 34.5 (range: 7-62 years), with 12 adults and 12 males. Trilineage dysplasia was present in 13 (81%). Marrow basophilia was seen in only two patients, one of whom had CML-BC. HLA-DR was positive in all 12 patients assessed, CD33 in 11, CD13 in 10, and CD34 in seven. Four patients had one other abnormality apart from the t(6;9). These were the t(9;22) in the patient with CML and deletion 9q, addition 13q, and an isochromosome 8q in the other three patients. There were no complex karyotypes. Fms-related tyrosine kinase 3--internal tandem duplication (FLT3-ITD) mutations were seen in seven of 13 patients. Follow-up details were available for six patients. Three received palliative care, and follow-up details were not available for the other seven. The response to chemotherapy was poor in the remaining patients. The only patients who survived were three out of the four who had allogeneic hematopoietic stem cell transplantation (HSCT).
Cancer genetics and cytogenetics 12/2010; 203(2):297-302. · 1.54 Impact Factor
