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Biomedical subjects

M Chandy

Publications and source records attributed to M Chandy.

At least 37 records · Page 2Linked to original sources
PubMed2004

Hematological and molecular remission with combination chemotherapy in a patient with PLZF-RARalpha acute promyelocytic leukemia (APML).

Patients with acute promyelocytic leukemia (APML) with the t(11;17) translocation usually respond poorly to all-trans retinoic acid (ATRA) and chemotherapy. We describe a patient with promyelocytic leukemia zinc finger/retinoic acid receptor alpha (PLZF/RARalpha) APML who was treated with combination chemotherapy after poor response to arsenic trioxide. He achieved hematological remission in 4 weeks followed by achievement of molecular remission in 8 weeks. Four cycles of consolidation chemotherapy followed by four cycles of maintenance therapy were given over a period of 9 months. At a follow-up of 32 months after achieving hematological remission, he continues to remain in hematological and molecular remission with normal blood parameters and negative reverse transcriptase polymerase chain reaction (RT-PCR) results. Combination chemotherapy can achieve sustained remission in patients with PLZF/RARalpha APML.

Adult↗
PubMed2004

Infections among allogeneic bone marrow transplant recipients in India.

SUMMARY: Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and allogeneic bone marrow transplantation (BMT) despite prophylaxis, use of growth factors and newer antimicrobial drugs. We report the clinical profile of infections among 297 patients who underwent 304 allogeneic transplants between 1986 and December 2001. All patients developed febrile neutropenia. There were 415 documented infections among 304 transplants. This included bacterial (34.9%), viral (42.9%), fungal (15.9%) and other infections (6.3%) including tuberculosis. Bacterial pathogens were mainly Gram-negative bacteria (80%) as compared to Gram-positive (20%) bacteria. The common Gram-negative bacteria were nonfermenting Gram-negative bacteria (NFGNB) (24.9%), Pseudomonas (17.9%), Escherichia coli (17.9%) and Klebsiella (9.7%). The major source of positive cultures was blood (53.7%) followed by urine (25.5%) and sputum (8.9%). In all, 133/304 (43.7%) transplants had 178 documented viral infections. The common viral infections were due to cytomegalovirus, herpes group of viruses and transfusion-related hepatitis; and 60/304 (19.7%) transplants had 66 documented fungal infections. Common fungi included Aspergillus species (69.7%), Candida (22.2%) and Zygomycetes (8.1%). Tuberculosis was documented in 2.3% of the transplants. Catheter infections were suspected or documented in 7.8% of the transplants (24/304). The incidence of infections in this series from developing countries is not significantly different from reports from the West. Bone Marrow Transplantation (2004) 33, 311-315. doi:10.1038/sj.bmt.1704347 Published online 1 December 2003

Adult↗
PubMed2004

Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience.

A total of 11 children (five males and six females) with hypergranular type of acute promyelocytic leukemia (APML) were treated with intravenous arsenic trioxide (As(2)O(3)) between December 1998 and October 2003. Eight cycles of As(2)O(3) (0.15 mg/kg/day) were administered (induction, consolidation and six cycles of maintenance) over a period of 12 months. The median WBC count at diagnosis was 3400/mm(3) (range: 800-9800). In all, 10 patients (91%) achieved hematological remission at a mean duration of 48 days (range: 41-60) with all 10 patients achieving molecular remission at a median duration of 81 days (range: 64-109). Toxicity was minimal with leukocytosis in six patients, ichthyosis and hyperpigmentation of skin in five and mild peripheral neuropathy in one patient. One patient who relapsed 6 months after completing therapy achieved a second hematological and molecular remission with As(2)O(3). With a median follow-up of 30 months (range: 4-62), the overall (OS) survival is 91% with a relapse-free survival (RFS) of 81%. As(2)O(3) achieves hematological and molecular remission in majority of newly diagnosed children with APML with minimal toxicity, but long-term follow-up is required to evaluate late effects of As(2)O(3) and study the minimum dose and duration required for a sustained remission.

Adolescent↗
PubMed2004

External fixators in haemophilia.

External fixators (EF) are not commonly used for patients with haemophilia. We describe the use of EF (Ilizarov, AO- uni- and bi-planar fixators and Charnley clamp) in nine patients (mean age: 19.2 years; range: 9-37) with haemophilia for the following indications - arthrodesis of infected joints, treatment of open fractures and osteoclasis. EF required an average of nine skin punctures [range: 4-17 were maintained for a period of 15 weeks (range: 8-29.5), without regular factor replacement, till bone healing was adequate and were removed with a single dose of factor infusion]. The mean preoperative factor level achieved was 85% (range: 64-102%). Much lower levels were subsequently maintained till wound healing. The average total factor consumption was 430 IU kg(-1) (range: 240-870), administered over a period of 17 days (range: 9-44). There were no major complications related to EF except in a patient who developed inhibitors. In conclusion, EF can be used safely in haemophilic patients who do not have inhibitors and does not require prolonged factor replacement.

Adolescent↗
PubMed2004

Informativeness of linkage analysis for genetic diagnosis of haemophilia A in India.

The objective of this study was to assess the frequency of factor VIII (FVIII) gene intron 1 and intron 22 inversions and the informativeness of polymorphic markers for the genetic diagnosis of patients with haemophilia A (HA). Fifty unrelated patients with HA were first assessed for the intron 1 and intron 22 inversion mutations. Inversion-negative families were then screened for the bi-allelic intragenic markers--intron 7 G-->A polymorphism, HindIII site in intron 19 and XbaI site in intron 22 and the multiallelic dinucleotide CA repeat alleles in introns 13 and 22. The extragenic, multiallelic VNTR DXS52 (st14) was also analysed. Intron 22 inversion mutation was found in 38% (n = 19) of all patients and 46% of those with severe HA. Intron 1 inversion was found in one (2%) patient. Of the 30 inversion-negative families, XbaI site polymorphism was the single most informative marker (70%, n = 21/30) followed by HindIII (60%, n = 18/30), intron 13 CA repeats (56.66%, n = 17/30), intron 22 CA repeats (50%, n = 15/30), DXS52 VNTR (23.33%, n = 7/30) and intron 7 G-->A polymorphism (6.66%, n = 2/30). The combined use of these markers was informative in 92% (n = 46/50) of HA families. Based on the informativeness of these markers a comprehensive algorithm has been proposed for genetic diagnosis of HA in India.

Chromosome Inversion↗
PubMed2003

Determination of the breakpoint and molecular diagnosis of a common alpha-thalassaemia-1 deletion in the Indian population.

The previously described South African type alpha-thalassaemia-1 mutation was identified in Indian HbH patients using a polymerase chain reaction (PCR) strategy. A multiplex PCR assay was devised to detect heterozygotes and homozygotes. This alpha-thalassaemia-1 mutation was found to be the commonest determinant causing HbH disease in this population. In one family this mutation was found in combination with a novel splice donor mutation alpha2 IVS I-1 (G-->A). Characterization of the breakpoint junction sequence revealed, in addition to a 23 kb deletion, that there was an addition of approximately 160 bp bridging the breakpoints. Similar to other deletions in the alpha-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion.

Adult↗
PubMed2002

Cytogenetic, fluorescent in situ hybridization & reverse transcriptase-polymerase chain reaction analysis in acute promyelocytic leukaemia patients.

BACKGROUND & OBJECTIVES: The presence of t(15;17) or PML-RAR alpha fusion transcript is the diagnostic hallmark of patients with acute promyelocytic leukaemia (APL). Cytogenetic (CG), fluorescent in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) are mainly the techniques used for detecting this abnormality. The objective of this study was to compare and assess the role of CG, FISH and RT-PCR in the diagnosis of APL. METHODS: CG, FISH and RT-PCR analysis were performed in 29 patients with APL (28 M3, 1 M3v; 27 studied at diagnosis and 2 at relapse). RESULTS: Karotypes obtained in 25 patients revealed t(15;17) in 21 normal karyotype in 3 and trisomy 8 in 1 patient. In 26 patients FISH was positive for PML-RAR alpha fusion in both interphase (IP) and metaphase, two were negative and one patient had no cells for FISH analysis. IP FISH confirmed the fusion of PML-RAR alpha in all patients with t(15;17) detected by CG. RT-PCR was positive in the 22 patients analyzed (7 patients did not have RT-PCR). PCR was positive in the 3 patients with cytogenetically normal karyotypes and in one patient when karyotyping was a failure. CG detected 21 (72.4%) patients with t(15;17) of which additional chromosomal abnormalities were detected in 20 per cent of patients with successful karyotype. INTERPRETATION & CONCLUSION: FISH and RT-PCR were useful in detecting PML-RAR alpha fusion in cytogenetically normal patients and those in when karyotyping was a failure and can be used in routine analysis for rapid confirmation of t(15;17) in patients with acute myeloid leukaemia.

Adolescent↗
PubMed2001

Polymyositis--an unusual manifestation of chronic graft-versus-host disease.

Polymyositis is a rare autoimmune manifestation of chronic graft-versus-host disease (GVHD) characterized by muscle pain, weakness, and an increase in muscle-related enzymes that responds well to treatment with immunosuppressive agents such as steroids and cyclosporine. We describe a case in which polymyositis was the main manifestation of chronic GVHD that occurred 12 months after allogeneic bone marrow transplantation in a patient with acute lymphocytic leukemia (ALL). The polymyositis responded well to treatment with steroids and cyclosporine, with no relapse of symptoms on tapering of the medication.

Adolescent↗
PubMed2001

Allogeneic bone marrow transplantation in the developing world: experience from a center in India.

We describe our experience of setting up an allogeneic BMT program at the Christian Medical College Hospital, Vellore over a period of 13 years, from October 1986 to December 1999. Two hundred and twenty-one transplants were performed during this period in 214 patients, with seven patients undergoing second transplants. Indication for BMT were thalassemia major - 106 (48%), CML - 30, AML - 35, ALL - 10, SAA - 22, MDS - six and six for other miscellaneous disorders. The mean age of this patient cohort was 15.6 years (range 2-52). Graft-versus-host disease of grades III and IV was seen in 36 patients (17%) and this was the primary cause of death in 20 patients (9.2%). All patients and donors were CMV IgG positive. Sepsis was the primary cause of death in 16 patients (7.4%), 10 bacterial, four fungal and two viral. One hundred and ten of this series of patients are alive and disease free (50%) with a median follow-up of 24 months (range 2-116). These results are comparable to those achieved for patients with similar disease status in transplant units in the Western world and cost a mean of US$15 000.

Adolescent↗
PubMed2001

Tuberculosis among allogeneic bone marrow transplant recipients in India.

Allogeneic bone marrow transplant recipients have severe impairment of cell-mediated immunity and hence a higher incidence of mycobacterial infections might be expected in regions where tuberculosis is common. We reviewed the case records of 217 patients who underwent allogeneic bone marrow transplantation during the period 1986-1999 at our center in India. Mycobacterial infections were diagnosed in three patients (1.38%). All patients presented with extrapulmonary disease. Two patients had disseminated tuberculosis with one of these being diagnosed on autopsy studies. The third patient had tuberculosis involving the cervical lymph node and dorsal spine. Two patients treated with antituberculous therapy are well. Infection with Mycobacterium tuberculosis is not a common problem in allogeneic bone marrow recipients even in an endemic area, but when it occurs, it is usually disseminated with predominantly extrapulmonary involvement.

Adult↗
PubMed2001

Evaluation of existing limited sampling models for busulfan kinetics in children with beta thalassaemia major undergoing bone marrow transplantation.

Busulfan pharmacokinetic parameters are useful in predicting the outcome of allogeneic bone marrow transplantation (BMT). Standard pharmacokinetic measurements require multiple blood samples. Various limited sampling models (LSM) have been proposed for reducing the sample number required for these measurements, essentially for patients with malignant disorders undergoing BMT. This study was undertaken to evaluate the existing LSM for busulfan pharmacokinetics to find out the most suitable method for patients with thalassaemia major undergoing BMT. Busulfan levels in plasma samples were analysed by HPLC. The AUC calculated by non-compartmental analysis using the program 'TOPFIT' was compared with previously published LSMs. Our seven sample pharmacokinetic data for AUC calculation was compared with the published LSMs. The three sample models suggested by Chattergoon et al and Schuler et al showed significant agreement with AUC TOPFIT (R(2) = 0.98 and 0.94, respectively) in our clinical context. Other models resulted in significant over or under representation of observed values (Vassal's model R(2) = 0.61; Chattergoon's two sample model R(2) = 0.84; four sample model R(2) = 0.83; Schuler's two sample model R(2) = 0.79). By these data the three sample LSM proposed by Chattergoon et al and Schuler et al are suitable for calculation of the AUC in patients with thalassaemia major undergoing BMT conditioned with oral busulfan.

Adolescent↗
PubMed2001

Glutathione S-transferase activity influences busulfan pharmacokinetics in patients with beta thalassemia major undergoing bone marrow transplantation.

Busulfan, at a dose of 16 mg/kg, is widely used in combination with cyclophosphamide as a conditioning regimen for patients undergoing bone marrow transplantation. Wide interindividual variation in busulfan kinetics and rapid clearance of the drug have been reported, especially in children. Some of the factors contributing to interpatient variability have been identified. They include circadian rhythms, age, disease, drug interaction, changes in hepatic function, and busulfan bioavailability. In this study, we demonstrate that hepatic glutathione S-transferase (GST) activity correlates negatively with busulfan maximum and minimum concentrations (Pearson's correlation r = -0.74 and -0.77, respectively) and positively with busulfan clearance (Pearson's correlation r = 0.728) in children with thalassemia major in the age range of 2 to 15 years. We also found that plasma alpha GST levels were 5 to 10 times higher in patients with thalassemia than in normal controls and age-matched leukemic patients, either reflecting extensive liver damage, elevated expression of the enzyme, or both in thalassemic patients. Plasma alpha GST concentrations showed a similar correlation with busulfan kinetic parameters to that observed for hepatic GST. The status of hepatic GST activity accounts, at least in part, for the observed interindividual variation in busulfan kinetics, while the observed association with plasma alpha GST is difficult to explain at present.

Adolescent↗
PubMed2001

A pilot study on the role of cytomegalovirus & human herpesvirus-6 infections in Indian bone marrow transplant recipients.

BACKGROUND & OBJECTIVES: Studies from Western transplant centers have shown the importance of cytomegalovirus (CMV) in infections among immunosuppressed post-transplant patients (both solid and bone marrow transplant recipients). Human herpesvirus-6 (HHV-6) infection is also important. Since such data are lacking from India, we carried out a pilot study to investigate the role of these two viruses in infections among Indian allogeneic bone marrow transplant (BMT) recipients. METHODS: A total of 21 BMT patients who developed acute graft versus host disease (GVHD), two patients who developed chronic GVHD, and eight recipients who did not develop GVHD but had skin rash/elevated liver enzymes, persistent cytopaenia or interstitial pneumonitis with a high clinical suspicion of possible CMV association were studied for markers of CMV and HHV-6 infections. RESULTS: CMV DNAemia was documented in 9 (42.8%) and CMV IgM in 4(19%) of the 21 patients with acute GVHD. HHV-6 DNAemia was not seen in any patient with acute GVHD but 2 (9.5%) had HHV-6 IgM. Of the 2 patients with chronic GVHD, 1 was positive for CMV DNA and IgM, and both were negative for HHV-6 markers. The lower incidence of CMV DNAemia in our recipients may be attributable to the presence of neutralizing antibody (anti gB/AD-1) among the 17 CMV and HHV-6 DNAemia negative recipients, 4(23.5%) had neutralizing antibodies (S/N ratio > or = 5). Of the 13 CMV DNAemia positive recipients, only one (7.7%) was positive for neutralizing antibodies. Among the 5 neutralizing antibody (S/N ratio > or = 5) positive recipients, 4 (80%) were negative for CMV DNAemia. The one nPCR positive was revealed only at high DNA (> 0.1 microgram) input indicating low CMV signal strength. INTERPRETATION & CONCLUSION: The present study shows the use of DNAemia in detecting CMV infections among BMT recipients. All recipients had high avidity CMV IgG (AI > 50%) confirming CMV reactivation or reinfection in these patients. There was evidence from this study suggesting that neutralizing antibodies may play a role in controlling CMV reactivation. We found no significant HHV-6 association with GVHD in Indian allogeneic BMT recipients.

Adolescent↗