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Biomedical subjects

M Irfan

Publications and source records attributed to M Irfan.

At least 19 recordsLinked to original sources

In-vivo purging with the anti-CD20 antibody rituximab along with standard allogeneic peripheral blood stem cell transplantation (PBSCT) for relapsed childhood pre-B acute lymphoblastic leukaemia (ALL).

This case report describes the use of Rituximab for in vivo purging (by intravenous infusion) in a 12 years old boy with second remission of pre-B ALL. It was followed by conditioning therapy consisted of Busulphan and Cyclophosphamide. rh-G-CSF primed stem cells from an HLA identical sibling donor were infused. Standard graft versus host disease prophylaxis was given. He engrafted within two weeks. He did not develop acute graft versus host disease (aGvHD) but localized chronic GvHD developed. He had been on regular follow-up at CMH, Rawalpindi and is in complete remission 13 months post-PBSCT with no evidence of chronic GvHD at present.

Antibodies, Monoclonal↗

Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in -vitro sensitivity data and clinical response to empirical antibiotic therapy.

OBJECTIVE: To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Paediatric bone marrow transplant unit at Bismillah Taqee Institute of Health Sciences and Blood Disease Center from September 1999 to May 2004. PATIENTS AND METHODS: All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. RESULTS: Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. CONCLUSION: Gram-negative infections predominated, Imipenem/ Amikacin found to be most effective therapy while a low mortality rate is recorded in our setting suggesting good infection control.

Anti-Bacterial Agents↗

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

OBJECTIVE: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. DESIGN: A single centre descriptive study. PLACE AND DURATION OF STUDY: Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. PATIENTS AND METHODS: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. RESULTS: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. CONCLUSION: Haematopoietic stem cell transplant programme can be developed in a developed country setting. Post transplant complications are similar to what have been reported in the developed countries. In endemic areas malaria could prove to be fatal if not recognised and treated early.

Adolescent↗

Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country.

SETTING: A university teaching hospital in Karachi, Pakistan. OBJECTIVE: To define the clinical characteristics and outcome of miliary tuberculosis (TB) patients from a low human immunodeficiency virus (HIV) prevalence country. DESIGN: Review of adult miliary TB patients admitted between 1994 and 2001. Clinical characteristics of those dying from miliary TB were compared with those of the survivors. RESULTS: Most of the 110 cases reviewed were middle aged or elderly, with a female preponderance. An underlying medical condition was present in 47%. Presenting symptoms were of several weeks' duration, and mostly constitutional (fever and weight loss). Common laboratory findings included anaemia (62%), lymphopaenia (71%), hyponatraemia (74%), elevated serum alkaline phosphatase (57%) and hypoalbuminaemia (92%). Typical miliary pattern was observed in 77% of radiographs. Sputum smear and culture were positive in respectively 36% and 52% of those tested. Biopsy was performed in selected patients. Mean hospital stay was 8.8 days, and mortality was 30%. Those who died were significantly older than survivors and had a more fulminant course. Presence of altered mental status, lung crackles, leucocytosis, thrombocytopaenia and the need for ventilation were associated with increased mortality. CONCLUSION: Miliary TB carries a high mortality. It should be considered in patients who present with prolonged systemic symptoms. A positive TB culture or biopsy is needed to establish a diagnosis.

Adolescent↗

Rapidly-progressive bronchiolitis obliterans organising pneumonia.

Bronchiolitis obliterans organising pneumonia is a clinicopathological syndrome characterised by indolent course of flu-like illness followed by cough, dyspnoea and fever, and responds well to steroid treatment. We describe a 76-year-old woman who presented with a short three-day history and progressed rapidly to respiratory failure. She was successfully treated with high-dose steroids.

Aged↗

Peripheral blood stem cell transplantation in children with beta-thalassemia major.

OBJECTIVE: To share the preliminary data on stem cell transplantation in Pakistan. DESIGN: This is a single center retrospective analysis of the outcome of allogeneic peripheral blood stem cell (PBSC) transplantation in b-thalassemia major patients. PLACE AND DURATION OF STUDY: Bismillah Taqee Blood Diseases Centre, Karachi; a tertiary care hematology center from September 1999 to September 2002. PATIENTS AND METHODS: Twelve patients with b-thalassemia major received allogeneic PBSC transplantation from HLA identical sibling donors except in one case where mother was the donor. All patients received busulphan and cyclophosphamide conditioning therapy and cyclosporin A/methotrexate for graft versus host disease (GVHD) prophylaxis. Donors were primed with G-CSF for 4 days and stem cells were harvested using Haemonetics MCS + cell separator on 5th day. All patients received G-CSF starting from day + 4 until their neutrophil count rose to normal. RESULTS: Engraftment was achieved in all patients except one who required a second dose of bone marrow graft on day +21. Median time to achieve absolute neutrophil count of > 0.5 x 10(9)/l was 9.0 days (range 8-31 days) and platelet count of > 20 x 10(9)/l was 14 days (12-35 days). Acute GVHD was seen in 3 patients, one patient had grade IV gut GVHD; another patient had grade III gut GVHD while third patient had grade II skin GVHD. Median hospital stay was 29 days. Six patients were well and transfusion independent 3 to 36 months posttransplant. One episode of primary graft failure required a second dose of bone marrow harvest. Another episode of graft rejection received two doses of donor lymphocytes infusion. There were 4 deaths due to grade IV gut GVHD because of uncontrolled systemic Candida infection and one due to hepatic veno-occlusive (VOD) disease. CONCLUSION: Allogeneic peripheral blood stem cell transplantation can be safely and economically carried out in Pakistan. Although there had been 4 deaths during 36 months follow-up, with increasing understanding and experience the outcome is expected to improve.

Child, Preschool↗

Allogeneic peripheral blood stem cell transplantation for aplastic anaemia: a single centre experience.

OBJECTIVE: To assess the feasibility of stem cell transplantation in local setting. SETTING: A tertiary care haematology centre. STUDY DESIGN: This is a single centre retrospective analysis of the outcome of allogeneic peripheral blood stem cell transplantation for severe aplastic anaemia. OBJECTIVES: Preliminary data on stem cell transplantation in Pakistan. PATIENTS AND METHODS: Aplastic anaemia is an uncommon disorder with a high mortality without treatment. Immunosuppression and bone marrow transplantation remains the mainstay of treatment. Stem cell transplantation facility became available in Pakistan in 1999, since then both allogeneic and autologous procedures are carried out for severe aplastic anaemia, b-thalassaemia major and haematological malignancies. Between April 2000 and July 2002, 20 allogeneic peripheral blood stem cell transplants were carried out for aplastic anaemia from HLA identical siblings. Donors were primed with G-CSF 10 mcg/kg/day subcutaneously for 4 days; stem cells were harvested on 5th day using Haemonetics MCS+ cell separator. Cyclophosphamide was used for conditioning; cyclosporin A and methotrexate were given for graft versus host disease prophylaxis. RESULTS: Eighteen out of 22 patients survived transplant in a follow up period of 788 days. The causes of death were intra-cranial haemorrhage on day +7, herpes encephalitis on day +180, graft failure and mucour mycosis on day +353 and TB meningitis on day +544. Allogeneic peripheral blood stem cell transplantation resulted in 81% event free survival in our hands. CONCLUSION: Allogeneic peripheral blood stem cell transplantation is feasible and life saving in an otherwise fatal disorder. This could be carried out effectively in Pakistan.

Adolescent↗

Primary myelodysplastic syndrome: clinical spectrum of 53 cases.

Fifty three (45 males, 8 females) patients with primary meylodysplastic syndrome were seen between January 1990 and June, 1996. Fifteen (28%) patients had refractory anaemia (RA), 9 (17%) refractory anaemia with ring sideroblast (RARS), 21 (40%) refractory anaemia with excess blasts (RAEB), 5 (9%) refractory anaemia with excess blasts in transformation (REABt) and 3 (6%) had chronic myelomonocytic leukemia (CMML). The mean age for the whole cohort was 59 years. Patients with RAEB and RAEBt were significantly younger than other FAB types with a mean age of 53.5 and 45 years respectively. Among the FAB types RAEB appeared to be over represented. Symptomatic anaemia (66% cases) was the major cause to seek medical attention. The commonest laboratory findings was anaemia; Hb < 8 g/dl in 31 (59%) patients. Only two patients had Hb > 12 g/dl at presentation. Twenty four (45%) patients had normocytic anaemia, mainly in RAEB group (61%). Macrocytosis was a dominant finding in patients with RA (53%) and RARS (53%). Bicytopenia (72%) was a more common finding than pancytopenia (8%). Bone marrow was normocellular in 32 (60%) patients and hypoplastic in 11 (21%). Dyserythropoiesis predominantly affected RA (80%), RARS (55%) and RAEB (43%) groups. Bilineage dysplasia (21%) was commoner than trilineage dysplasia (19%). Increased bone marrow fibrosis was seen in about half of the available trephines, mainly in RAEB patients. Median survival of patients was ten months with a follow up duration of 2-55 months. Four patients transformed to acute leukemia (M1 or M2) and died subsequently. However, infection was major complication and cause of death (10 cases). The preponderance of younger people to acquire the disease (especially the RAEB and RAEBt variants), the emergence of RAEB as the major group of MDS and increased prevalence of hypoplastic MDS point towards non-therapeutic genotoxin (s) in the causation of disease. Shortened survival and low rate of acute transformation points that patients did not withstand cytopenias and died earlier.

Adolescent↗

Warfarin and the apparent minor head injury.

Two cases of patients on warfarin who developed intracranial haematoma after an apparently minor head injury are described. There is a 10-fold increase in the likelihood of developing an intracranial haematoma in these patients. Recommendations are made regarding the management of this type of patient seen in the accident and emergency department.

Aged↗