Armed Forces Bone Marrow Transplant Research Articles

MAGNITUDE OF VANCOMYCIN RESISTANT ENTEROCOCCUS FECAL COLONIZATION AND BACTEREMIA IN PATIENTS WITH HEMATOLOGICAL DISEASES AT TERTIARY BONE MARROW TRANSPLANT CENTRE RAWALPINDI

Objective: To discover the frequency of vancomycin resistant enterococci (VRE) fecal colonization and subsequent bacteremia in patients with hematological diseases in a bone marrow transplant center.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), in collaboration with Armed Forces Bone Marrow Transplant Center, Rawalpindi, from Jan 2016 to Dec 2019.
 Methodology: Stool specimens/anal swabs from all enrolled patients were collected aseptically and transported to the laboratory without delay. Blood cultures were collected aseptically from only those enrolled patients who developed signs and symptoms of bacteremia. Stool and blood cultures were processed as per standard microbiological protocols. Enterococci were identified to species level by colony morphology and biochemical tests. Modified Kirby Bauer disc diffusion method and VITEK-2 system (Version-8.01 bio Merieux, France) were used to perform antimicrobial sensitivity of each isolate.
 Results: A total number of 246 patients were studied. Among them, 67 (27%) patients had fecal colonization by vancomycin resistant enterococci. We report a statistically significant association of recent hospitalization, prolonged exposure to antimicrobial therapy, chemotherapy exposure and use of indwelling devices during the hospital stay with vancomycin resistant enterococci colonization. Vancomycin resistant enterococci bacteremia was detected in 57 (23%) patients. Among these 57 patients, 53 (93%) were vancomycin resistant enterococci colonizers. Vancomycin resistant enterococci colonization was significantly associated with vancomycin resistant enterococci bacteremia.
 Conclusion: A considerable burden of vancomycin resistant enterococci fecal colonization exists among patients with hematological diseases. vancomycin resistant enterococci colonization poses a considerable risk of vancomycin........

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN FANCONI ANEMIA; A SINGLE CENTRE EXPERIENCE

Objective: To determine the treatment outcome of Hematopoietic stem cell transplantation in Fanconi Anemia.
 Study Design: Case series.
 Place and Duration of Study: Armed Forces Bone Marrow Transplant Center, Rawalpindi, from Jan 2001 to Jun 2018.
 Methodology: Data of all Fanconi anemia patients who had fully HLA matched bone marrow transplant during this period was analysed for variables affecting the outcome in terms of overall survival. Those fanconi anemia patients who had myelodysplastic changes or acute myeloid leukemia were excluded.
 Results: Total 27 patients underwent fully HLA matched allogeneic bone marrow transplant for Fanconi Anemia. Mean age of patients at transplant was 12.12 ± 5.16 years. All patients at transplant were in aplastic phase. Conditioning was done with fludarabine 120mg/m2 , ATG 20 mg/kg and Cyclophosphamide at a dose of 20-40 mg/kg. Mean time to neutrophil engraftment was 12.3 ± 2.92days and for platelets 20 ± 10.3 days. Major posttransplant complications were neutropenic fever in 26 (96%), hypertension in 18 (66.6%), mucositis in 12 (44.4%), azotaemia in 8 (29.6%), gut toxicity in 7 (25.9%) and haemorrhagic cystitis in 5 (18.5%) patients. Four patients (14.8%) had acute graft versus host disease while 7 (26%) patients had chronic GVHD. Overall survival at 6 months, 1, 5 and 8 years was 67%, 63%, 59% and 55% respectively. While overall survival in patients transplanted at younger age (<11 years) was 81.8% compared to 37.5% in older age group (>11years) and was statistically significant (p-value = 0.03).
 Conclusion: Our study demonstrated...................

HIGH ALTITUDE AND VENOUS THROMBOSIS: FREQUENCY AND RISK FACTORS

Objective: To determine the effect of high altitude on frequency and risk factors of venous thrombosis inindividuals ascending to high altitude
 Study Design: Cross-sectional analytical study.
 Place and Duration of Study: Armed Forces Bone Marrow Transplant Centre, Combined Military HospitalSkardu, from Apr 2015 to Aug 2018.
 Methodology: High Altitude was taken as height equal to or more than 8000 feet. Polycythemia as hemoglobin>16.5 g/dl OR hematocrit >49%. Medical records of all patients evacuated from high altitude through CombinedMilitary Hospital Skardu were analyzed retrospectively. A proforma was designed to include necessary variables.
 Results: We evaluated medical records of 539 individuals and found frequency of 86 (15.9%) for venous thromboembolism (VTE) at high altitude. Cerebral venous sinus thrombosis (CVST) was most common thrombotic complication seen in 39 patients (46%). Majority of thrombotic episodes occurred at >18000 feet (likelihood ratio (LR) 5.99, p-value 0.009). Majority of thrombotic episodes 34 (39%) occurred within first 45 days of ascent to high altitude. Thrombosis was linked to smoking 47 (55%) (likelihood ratio 21.3 and p-value <0.001) and use of melted snow as a source of drinking water 56 (65%) (likelihood ratio 57.6 and p-value <0.001).
 Conclusion: This study showed a very high frequency of thrombotic complications at high altitude. There isa need for a robust prospective study covering epidemiology, clinical information and diagnostics in order todevelop appropriate standard operating procedures and guidelines for prevention of thrombosis at HA

Frequency and Antifungal Susceptibility Pattern of Candida Species Causing Candidemia in Bone Marrow Transplant Unit

To determine the frequency and antifungal susceptibility pattern of Candida species causing candidemia or blood stream infections (BSI) in immunocompromised patients of a bone marrow transplant unit. The study was conducted at the Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Armed Forces Bone Marrow Transplant Center (AFBMTC), Rawalpindi, from 1st June 2019 to 31st December 2019. A total 256 paired blood culture samples from patients of all ages, irrespective of gender were collected during a period of seven months. The samples were processed as recommended Clinical & Laboratory Standard Institute (CLSI) guidelines. Antifungal susceptibility by break point MICs was performed through VITEK® 2 system (version: 08.01) for Fluconazole, Itraconazole and Amphotericin B. Of the total 256 blood cultures, 46 (17.97%) were positive for Candida species. The susceptibility of C. albicans was 100% to Amphotericin B, 90% to Fluconazole and 10% to Itraconazole, while C. tropicalis showed sensitivity of 92%, 88% and 0% against Amphotericin B, Fluconazole and Itraconazole, respectively. C. parapsilosis was found sensitive to Amphotericin B while resistance to Fluconazole and Itraconazole.Frequency of candidemia among immunocompromised patients is 17.9%. C. tropicalis and C. albicans are the two most common Candida species involved in blood stream infections in our setup. Fluconazole and Amphotericin B, both were found susceptible and can be used as empirical therapy.

Donor Chimerism Study by Single Nucleotide Polymorphism using SYBR green based Real Time PCR.

Objective:To optimize and evaluate a real time PCR of Single Nucleotide Polymorphism by SYBR Green method for detection of donor chimerism after haematopoietic stem cell transplantation.Methods:This descriptive study was conducted at Genetic Resource Centre (GRC) Lab Rawalpindi from Oct 2017 - Dec 2019. A total of twenty patients of post haematopoietic stem cell transplant with various haematological disorders were studied to see the status of donor chimerism by using SNP real time PCR using SYBR Green method and short tandem repeat PCR. These patients had undergone allogeneic HSCT from HLA-matched sibling donors at Pakistan Institute of Medical Science and Armed Forces Bone Marrow Transplant Centre.Results:Real time PCR using SYBR Green was able to detect significant amount of chimerism in all 20 patients having undergone HSCT. Regarding precision of the real time PCR assay the mean value of donor chimerism was 94.1% (SD 3.96) and by STR PCR it was 95.1% (SD 1.41). The assay was found to be sensitive with a detection limit of <1%.Conclusion:Our results demonstrate that SNP analysis by SYBR Green real time PCR may be used for the evaluation of chimerism status in patients having undergone HSCT with a sensitivity of <1%. Hence donor chimerism by this sensitive method can be used in monitoring of chimerism in post-transplant patients with various haematological disorders.

Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplant Recipients in High Endemic Population

Background: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). It causes end-organ disease, multi-organ dysfunction syndrome, graft failure, increased susceptibility to infections and GVHD. According to the published western data greatest risk of CMV infection is the seropositivity of the recipient, however, in a high endemic population where seropositivity is up to 100%, risk factors for CMV reactivation are different and are analyzed in this study. Methods: It is a prospective descriptive study performed at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan from January 2017 to March 2020. Consecutive patients who underwent allogeneic HSCT during this period were enrolled. All patients were prospectively monitored for CMV reactivation by weekly or two weekly CMV DNA quantitative PCR, from engraftment till day 100 post-transplant. CMV infection was diagnosed on detection of more than 200 copies/ml on PCR. Threshold for starting preemptive antiviral therapy was kept at 2000 copies/ml. Patients with past history of CMV infection, those who expired before day 14 post-transplant or those with less than 70% of required CMV tests were not included in the study. Factors associated with CMV reactivation, outcome of antiviral therapy and effect of CMV on post-transplant survival were studied. Results: Out of 319 transplants during this period, 230 patients fulfilled the inclusion criteria. Of these, 197 were HLA matched sibling, 18 were matched family donor and 15 were haploidentical transplants. There were 163 males and 67 females. Median age at transplant was 9.5 years (0.5-53). Eighty-three transplants were done in thalassemia, 55 in aplastic anemia, 14 in Fanconi anemia, 27 in acute leukemias, 8 in CML, 9 in MDS, 12 in HLH and 22 in other hematological disorders. All the patients and donor were CMV IgG seropositive when tested before transplantation. CMV reactivation was seen in 152 out of 230 patients (66.1%). Of 152, 95 patients had CMV viral load more than 2000 copies/ml and required antiviral treatment. Median time to reactivation since transplant was 35 days (13-90). In multivariate analysis using binary regression, risk factors for high viral load CMV reactivation included steroid administration (p=0.009), recipient age less than 10 years (p=0.003) and haploidentical transplant (p=0.048). No statistically significant association was found with the use of ATG, GVHD, underlying disease, ABO blood group or gender mismatch. Survival analysis using cox regression showed significant impact of high viral load CMV reactivation on post-transplant survival. Event-free survival (EFS) with and without CMV reactivation was 70.5 % and 89.7% respectively (p=0.004) and overall survival (OS) was 80.0 % and 97.4 % with and without CMV reactivation respectively (p=0.002). Valganciclovir was given in 89 patients and 6patients were treated with ganciclovir. Mean time to clear viremia was 19.8±9 days. Myelosuppression was seen in 41% of patients treated with valganciclovir. Renal impairment was seen in 25% of patients treated with valganciclovir. One patient had resistant disease. One patient had CMV pneumonia and she recovered. One patient died of suspected CMV pneumonia Conclusion: CMV reactivation was seen in 66.1% of the transplant recipients, this is higher compared to the western world due to high CMV seropositivity is this region. Steroids administration in post-transplant period significantly increase the risk of CMV reactivation. Preemptive therapy with valganciclovir effectively treats CMV reactivation. Viral threshold for treatment should be decided considering the regional endemicity. CMV adversely effects the transplant outcome in terms of EFS and OS. Disclosures No relevant conflicts of interest to declare.

Bortezomib-based Triplet Regimens for Remission Induction in Multiple Myeloma.

To compare the efficacy and side effect profile of different bortezomib-based triplet regimens for remission induction in patients with multiple myeloma (MM). Observational study. Armed Forces Bone Marrow Transplant Centre, Rawalpindi from January 2014 to December 2018. A total of 81 patients of MM, were registered from January 2014 to December 2018. In final analysis, 44 out of 81 patients were included as per inclusion/exclusion criteria. Bortezomib-based regimens were used either as first line (in newly diagnosed) or as second line (in relapsed/refractory bortezomib naïve patients) therapy. Three different bortezomib-based triplet therapies were used (1) VCd, (2) VRd and (3) VTd. As there were only two patients in VTd regimen group so for study purposes VRd and VTd were grouped together, i.e. Vd with an IMiD. Response to treatment was assessed using the IMWG criteria. Comparison between different bortezomib-based regimens was performed in terms of their tolerability and response rate after four cycles of chemotherapy. Out of 44 patients, 79.5% (n=35) patients received bortezomib-based triplet regimen as first line therapy, and in 20.5% (n=9) patients as second line therapy. VCd was administered to 56.8% (n=25) and Vd with an IMiD was used in 43.1% (n=19, VRd in 17 and VTd in 2) of the patients. Response was assessed at the end of fourth cycle. Overall response rate was comparable in both groups, 88% in VCd versus 89.4% in Vd with an IMiD group (p=0.432). In VCd and Vd with an IMiD group, CR was observed in 52% (n=13) and 57.9% (n=11) patients, respectively. Disease remained stable in 6.8% (n=3) patients. Treatment was generally well tolerated. Comparative analyses of both treatment groups revealed that the frequency of peripheral neuropathy was significantly higher in Vd with an IMiD group (47.3% vs 8% p=0.03). Grade III/IV neuropathy observed in 15.7% (n=3) of the patients in Vd with an IMiD group vs none in VCd group. Grade III/IV cytopenias were more seen in VCd group then in Vd with an IMiD group (16% vs. 5.2% p=0.16). The overall response rates were comparable in VCd and Vd with IMiD, with a better side effect profile seen with VCd regimen. Key Words: Multiple myeloma, Bortezomib, Triplet therapy, Remission induction, Peripheral neuropathy.

Epidemiology of aplastic anemia: a study of 1324 cases

ABSTRACT Objective: Prevalence of aplastic anemia (AA) is high in the Asian population. This study was done to explore the etiology and association of AA with various socio-economic and environmental factors. Study design and setting: Study included 1324 consecutive AA cases registered at Armed Forces Bone Marrow Transplant Centre Rawalpindi, Pakistan, from March 2001 to August 2016. The study questionnaire was completed through an interview. It included patients’ socio-demographic details, personal and family medical history, environmental attributes and clinico-hematological features. Results: The median age of patients was 20 years, 997 were male and 327 female. Distribution of non-severe, severe and very severe AA was 230 (17.4%); 598 (45.2%) and 496 (37.4%), respectively. The majority of patients were from low (n = 761, 57.5%) or middle socioeconomic class (n = 543, 41%). Consanguinity among patients (n = 806, 61%) was slightly higher than the national statistics. History of chemical exposures included fertilizers (n = 116, 8.7%), pesticides (n = 56, 4.2%) and industrial chemicals (n = 37, 2.8%). PNH clone was found in 63 of AA patients. After excluding 298 patients undergoing HSCT and 660 deaths/lost to follow-up, disease evolution was observed in 38(10.4%) patients out of 366 evaluable patients. These included PNH = 18, MDS = 11 and AML = 9. Discussion: Due to lack of funding and adequate human resource at the center, age and sex-matched controls could not be included. Other limitations were a lack of molecular testing to exclude the possibility of inherited bone marrow failure syndromes on a genetic basis. Conclusion: Younger age, male predominance and higher consanguinity point toward genetic factors in AA etiology among the South Asian population.

Allogeneic Haematopoietic Stem Cell Transplantation for Beta Thalassaemia Major in Pakistan: Outcome of 186 Cases

To analyse outcome of allogeneic haematopoietic stem cell transplantation (HSCT) in patients of beta thalassaemia major treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. The study included 186 consecutive beta thalassaemia patients undergoing HSCT from HLA matched related donors from October 2001 to December 2014. A comparison of conditioning regimens was made between long protocol (HU30mg/kg/day Azathioprine 3mg/kg/day, FLU 150, Bu14, Cy160) and Bu14/Cy200 both with or without Thiotepa, using overall and disease free survival (OS and DFS) as primary endpoints with rejection, acute and chronic GVHD as secondary end points. The study included 124 male and 62 female patients. Median age was 50 months (range 20 months to 13 years). Mean serum ferritin level before transplant was 1912 μg/L (range 426 to 5000). Patients were stratified as class I (n=49), II (n=62), and III (n=75) respectively as per Pesaro risk classification. Ninety three patients received conditioning with long protocol and same number of patients received Bu14/Cy200 conditioning regimen. Thiotepa was given to 38 patients (33 on long protocol and 5 on Bu14/Cy200). At a median follow up of 1683 days OS and DFS were 80.6 % and 69.4% respectively. In patients receiving long protocol OS, DFS and rejections were 85%, 72% and 15% respectively, whereas, in Bu14/Cy200 group OS, DFS and rejections were 76%, 66.7% and 11.8% respectively. Patients receiving Thiotepa during conditioning had lesser rejections (1/38) compared to those receiving conditioning without thiotepa (24/124) p=0.03. Eighty-five (45.7%) patients developed acute GVHD and 7 (3.8%) cases had chronic GVHD. Long conditioning protocol was found to be associated with better survival in beta thalassaemia patients undergoing allogeneic HSCT. Addition of thiotepa to conditioning regimen significantly reduced incidence of graft rejection.

Outcome of allogeneic haematopoietic stem cell transplantation in aplastic anaemia.

To analyze factors associated with survival, rejection and graft versus host disease in aplastic anaemia patients undergoing allogeneic haematopoietic stem cell transplantation (SCT) from HLA matched sibling donors. Analytical study. Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to June 2010. Consecutive aplastic anaemia (AA) patients undergoing haematopoietic stem cell transplantation from HLA-matched sibling donors at this centre were included in this study. Potential factors affecting overall survival, rejection, disease-free survival and graft versus host disease were analyzed. Survival analysis was done by Kaplan-Meier method. Cox regression model was applied for multivariate analysis. Ninety male and thirty-five female patients with AA were included in the study. Median age was 18 years. Conditioning regimens used were cyclophosphamide (Cy) plus antilymphocyte globulin (ALG) or antithymocyte globulin (ATG), fludarabine (FLU) +Cy+ATG, Campath 1-H +Cy in 89, 30 and 6 cases respectively. GVHD prophylaxis used was ciclosporin (CSA) plus prednisolone and short methotrexate in 81 while 44 received CSA plus prednisolone. At a median follow-up of 1185 days OS and DFS were 84% and 78% respectively. Factors associated with better OS were male sex, Flu/Cy/ATG conditioning and use of bone marrow as stem cell source. Flu/Cy/ATG conditioning regimen, bone marrow as stem cell source and CSA, prednisolone and short methotrexate regimen were associated with better survival in AA.

The stem cell transplant program in Pakistan—the first decade

Stem cell transplantation is curative in a number of otherwise fatal hematological diseases. In Pakistan, SCT was started in October 1995 at Dr Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over 350 allogeneic stem cell transplants have been carried out in these latter two centers. Another 50 autologous procedures were carried out in all centers. In 2004, a third center started transplants at the Aga Khan Hospital. The main indications for transplant are aplastic anemia, beta-thalassemia major and hematological malignancies. HLA-identical sibling donors provide stem cells for the recipient. In 70% of cases, a matched donor is identified. In sharp contrast to the rest of the world, the majority of transplants are allogeneic, donor-recipient pairs are CMV positive and fungal infection, tuberculosis and malaria are particular problems. The early results are promising, with transplant-related mortality reported to be 10-20%, whereas long-term survival is reported to be 78, 72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively. Financial constraints, poor socioeconomic status, poor transfusion services, trained human resources and difficulty in keeping pace with technological advances are major hurdles in the growth of transplant medicine. Government support is badly needed to strengthen existing facilities and to develop more centers.

Bone marrow transplant cure for β-thalassaemia major: initial experience from a developing country

Between July 2001 and June 2007, 48 consecutive patients with beta-thalassaemia major received allogeneic haematopoietic stem cell transplants (allo HSCT) from human-leukocyte-antigen-matched siblings at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, using standard conditioning regimens. The median age of the patient cohort was 4 years (range, 1-14 years). Thirty-one patients were in risk class I, 11 in class II and six patients were in class III. Engraftment was achieved in all patients. Survival was calculated from the date of transplant to death or last follow-up. Major post-transplant complications encountered were acute graft versus host disease (Ac GvHD) (grades II-IV), 35.4%; chronic GvHD, 8.3%; haemorrhagic cystitis, 12.5%; veno-occlusive disease (VOD) of the liver, 6.2%; bacterial infections, 37.5%; fungal infections, 19%; cytomegalovirus (CMV) infection, 6.2%; herpes infection, 6.2%; and tuberculosis in 2% of patients. Graft rejection was observed in five patients. Three patients received second transplants. Mortality was observed in 20.8% of patients. Major fatal complications included GvHD, VOD, intracranial haemorrhage, septicaema, CMV disease and disseminated tuberculosis. Overall survival and disease-free survival were 79% and 75%, respectively, at 6 years post-HSCT.

Comparison of Different Chemotherapy Regimens in the Management of Acute Myeloid Leukaemia - 5 Years Experience from Pakistan.

OBJECTIVES: This is a retrospective study in acute myeloid leukaemia (AML) patients carried out at Armed Forces Bone Marrow Transplant Centre Rawalpindi Pakistan between July 2001 and June 2006. Aim of the study was to evaluate outcome in AML patients treated with different remission induction and consolidation chemotherapy regimens in our population.METHODS: During 5 years period between July 2001 to June 2006, 46 patients received treatment for AML at our centre. Twenty nine patients were males and 17 were females. Median age of patients was 21 years (range: 7–56 years). These 46 patients were categorized into two groups on the basis of type of leukaemia and chemotherapy given. In group-I 40 patients (group Ia: 23 patients of M1–M6, less M3 group Ib: 17 patients of AML M3) received anthracycline and cytarabin based chemotherapy. In group- II, six patients (AML- M3) received all trans retinoic acid (ATRA) based chemotherapy.RESULTS: In group Ia, out of 23 patients, 14 patients (60.8%) achieved complete remission (CR) after remission induction chemotherapy,10 patients remained in CR after 3rd and 4th consolidation. Eleven patients died and five patients relapsed during treatment and follow up. In this group overall CR, relapse rate (RR) and mortality was 30.4% (7/23), 21.7% (5/23) & 48% (11/23) respectively. In group Ib out of 17 patients, 9 patients (53%) achieved CR after remission induction. Eleven patients died during treatment while one patient relapsed in this group. Overall CR, RR & mortality was 29.4% (5/17), 6% (1/17) & 55% (11/17) respectively. In group II all patients achieved CR (100%) after 1st course of chemotherapy. Two of these patients unfortunately died of uncontrolled sepsis during 1st consolidation, while remaining 4 patients 66.6% are on maintenance chemotherapy and are still in CR.CONCLUSION: Overall CR, RR and mortality in all groups was 35% (16/46), 13% (6/46) and 52% (24/46) respectively at a median follow-up of 36 ± 8 months. Survival in AML-M3 patients treated with ATRA based chemotherapy is significantly superior than anthracycline based chemotherapy (66.6% vs 29.4%). Infection and chemotherapy toxicity being major causes of mortality.

Bone Marrow Transplant Activity - A Country Report from Pakistan.

Bone Marrow transplant activity started in 1999 in Pakistan when Bismillah Taqee Institute of Health Sciences & Blood Diseases Centre started functioning in the southern port city of Karachi, Pakistan. Two years later in year 2001 Armed Forces Bone Marrow Transplant Centre started functioning in the northern part of country, Rawalpindi, Pakistan. In 2004 another transplant centre, started in Aga Khan University Hospital, Karachi, Pakistan. Since the establishment of these transplant centers a total of 349 allogeneic transplants have been carried out for various hematological disorders. The major indications included aplastic anaemia (n=166), β-Thalassaemia major (n=76), chronic myeloid leukaemia (n=57), acute leukaemias (n=37) and misc disorders including MDS, Fanconi anaemia and others (n=13). A total of 22 autologous transplants in lymphomas and multiple myeloma have also been carried out. Since this number is very small, only data of allogeneic transplants is being presented here. Major post transplant complications encountered were neutropenic fever in 92.6% patients with 27% culture positivity (412/1571). Infective complications included bacterial infections (both gram+ive and gram-ive) in 194 patients (56%), fungal infection in 32 patients (10%), CMV infection in 15 patients (5%), herpes infection in 16 patients (5%), tuberculosis in 9 patients (3%) and PCP in 1 patient (0.28%) and malaria in 1 patient (0.28%). So post transplant infections were confirmed in 76.6% (268/349) patients on the basis of clinical assessment, microbiological, virological and histopathological analysis. Non infective post transplant complication included aGvHD (grade II-IV) in 80 patients (23%), cGvHD 46 patients (13.1%), VOD liver in 25 patients (7.2%), haemorrhagic cystitis in 27 patients (7.7%), ARF in 13 patients (3.7%), primary graft failure in 5 patients(1.4%), graft rejection in 17 patients (4.9%) and relapse in 14 patients (4%). Transplant related mortality was observed in 93 patients (26.6%). Infective & non infective causes of mortality included septicemia in 15 patients (4.3%), CMV in 8 patients (2.3%), fungal infections in 8 patients (2.3%), tuberculosis in 2 patient (0.6%). herpes encephalitis in 1 patient (0.3%) VOD in 8 patients (2.3%), aGvHD in 12 patients (3.4%), cGvHD in 7 patients (2.0%), ARF in 8 patients (2.3%) and intracranial haemorrhage in 3 patients (0.9%). Graft related mortality due to graft failure and relapse was observed in 6 patients (1.7%) and 14 patients (4%) respectively. Unrelated accidental death in 1 patient (0.3%). Overall survival was observed in 256 patients (73.3%) and DFS in 250 patients (71.6%). The OS and DFS was 72.7% and 70.9% in BTIHS & BDC patients, whereas OS & DFS was 72.8% and 70.7% respectively in AFBMTC patients. The OS & DFS was 82.6% at AKUH. Disease wise overall survival in aplastic anemia, β-Thalassaemia, CML and acute leukemia was 78.3%, 76.3%, 63.1% and 59.5% respectively.

Post Allogeneic Stem Cell Transplant Complications - Single Centre Experience from Pakistan.

Over last five years 154 patients received HLA matched sibiling transplants at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. Indications for transplant included Aplastic anemia, B-Thalassaemia major, Chronic Myeloid leukemia, Acute leukemias, and miscellaneous disorders which included Myelodysplastic syndrome, Fanconi's anemia, Non-Hodgkin lymphoma, and Gaucher's disease. All patients received standard conditioning regimens and GvHD prophylaxis. Pre-transplant infection surveillance was carried out in all patients and strict prophylaxis against infection was observed as per our transplant policy. During post transplant follow up we encountered certain infective and non infective complications. These included: acute GvHD (grade II–IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jiroveci infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. We encountered certain rare unexpected post transplant complications which have been rarely reported in literature before. These included Hickman catheter embolization, Guillain Barre syndrome, co-infection with pneumocystis jirovicii and a rare fungus trichosporon beigilii, cyclosporine induced uncontrolled seizures, idiopathic polycythemia, haemorrhagic pericardial effusion with cardiac temponade, deep vein thrombosis, dengue fever and measles. These complications were effectively managed in our centre. There was only one death associated with these complications. Mortality was observed in 27.2% patients. Mortality related to non-infective complications was 14.2%. Major non-infective causes of mortality were GvHD, VOD, disease relapse, intracranial haemorrhage and acute renal failure. Mortality related to infections was 13%. Fatal infections included CMV disease, disseminated aspergillosis, pseudomonas septicaemia and tuberculosis.

Haematopoietic Stem Cell Transplantation - An Experience from Developing World.

One hundred and fifty four patients received allogeneic stem cell transplant from HLA matched siblings for various haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to Sep 2006. Indications for transplant included aplastic anaemia (n=66), b-thalassaemia major (n=40), CML (n=33), acute leukaemia (n=8) and misc disorders (n=7). One hundred and twenty patients were male and thirty four were female. Median age of patient cohort was 14 yrs (range 1 ¼ −54 yrs). Pre-transplant infection surveillance was carried out and strict prophylaxis against infection was observed. The mean mononuclear cell dose was 4.2 x 109/kg of recipient. Post transplant complications encountered in our patients were: acute GvHD (grade II-IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jirovici infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. Certain unexpected rare post transplant complications were also observed in our patients. These included hickman catheter embolization, GB syndrome, deep vein thrombosis, haemorrhagic pericarditis with clots leading to cardiac temponade, idiopathic polycythemia, dengue fever and status epilepticus. Mortality was observed in 27.2% patients. Major causes of mortality were GvHD, VOD, relapse, intracranial haemorrhage, acute renal failure, pseudomonas septicemia, tuberculosis, disseminated aspergillosis and CMV infection. At five years, the overall survival (OS) and disease free survival (DFS) was 72.5% & 70.7% respectively.

Post-transplant infections: single center experience from the developing world

To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.

Allogeneic bone marrow transplantation in β-thalassaemia—single center study

Objective: To evaluate outcome of allogeneic BMT in β-Thalassaemia at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from August 2001 to November 2003. Methods: Nineteen patients with β-Thalassaemia underwent allogeneic BMT/PBSC transplantation from HLA identical sibling donors. Patients were classified in three groups according to Pesaro (Italy) risk classification. Class-I(n=9) and Class-II(n=7) patients received conditioning with busulphan/cyclophosphamide, whereas Class-III(n=3) patient received conditioning with hydroxyurea, azathioprine, fludarabine, alongwith Bu14/Cy 200. Cyclosporine, prednisolone and methotrexate were given for GvHD prophylaxis. Stem cells dose infused was >4.0x108/kg body weight of the patient. Results: Engraftment was achieved in all Class-I patients, whereas in Class-II and Class-III , graft rejection was observed in one patient from each class. Median time to achieve absolute neutrophil recovery (> 0.5 x109/l) was 13 days, platelet count (>20 x109/1) was 15 days and reticulocyte count (> 0.5%) was 15 days. Acute GvHD was observed in 15 patients. One patient developed grade IV GvHD (liver and skin) and died within 30 days post BMT. Post transplant infectious complications were pseudomonas septicemia, disseminated fungal infection, CMV pneumonia and tuberculosis. Three patients died of these complications during post transplant period (3190 days). Median stay in hospital was 25 days. Conclusion: Allogeneic BMT is the only curative therapy for β-Thalassaemia patients, however the success rate can be increased if the patients are selected carefully and transplanted at an early age (JPMA 54:499;2004).

Frequency of tuberculosis in haematological malignancies and stem cell transplant recipients.

To assess magnitude of tuberculosis (TB) in patients suffering from various haematological malignancies and stem cell transplant (SCT) recipients. Descriptive study. Oncology Department, Combined Military Hospital, Rawalpindi, and Armed Forces Bone Marrow Transplant Centre, Rawalpindi, from July 2001 to December 2002. Patients suffering from various haematological malignancies treated between July 2001 and December 2002 were included in the study. The hospital records and out-patient follow-up charts were reviewed for demographic information, diagnosis, clinical presentation, laboratory investigations, radiological and pathological examinations, sites involved in TB, methods of diagnosis, number and type of anti-tuberculosis drugs given and response to treatment. During the study period a total of 213 (including 25 allogeneic stem cell transplant (SCT) recipients) patients with different haematological disorders were treated. Out of these, 34, including 4 SCT recipients developed tuberculosis. Overall frequency of TB was 16 %. Median age of TB patients was 33.5 years (range 8-80 years). Median time between diagnosis of haematological disorders and tuberculosis was 21 weeks. Sites of involvement by TB were lung (18), disseminated (6), lymph node (5), pleura (2), spine (2) and pericardium (1). Three of the patients died of TB; one undiagnosed, second with multi-drug resistant TB and the third soon after the start of anti-tuberculosis treatment while remaining 31 cases responded to anti-tuberculosis treatment. Tuberculosis is a major problem in immunocompromised patients and there is need to establish guidelines for TB chemoprophylaxis in our setup.

Central venous catheter-related bloodstream infections in cancer patients.

To determine the frequency of central venous catheter-related bloodstream infections (CR-BSI) in cancer patients and the antimicrobial susceptibility pattern of the isolates. A cross-sectional study. The study was conducted between April 2002 and March 2003 at the Armed Forces Institute of Pathology, Rawalpindi in collaboration with Oncology Units of Armed Forces Bone Marrow Transplant Centre and Combined Military Hospital, Rawalpindi. Cancer patients requiring short or long-term central venous catheterization at the time of admission or thereafter were included. Catheter tips on removal were cultured quantitatively; specimens of blood and pus were cultured qualitatively. Isolates were identified and antimicrobial susceptibility testing was performed by standard techniques. Eighty-nine patients were included in the study. The frequency of CR-BSI was 17%. Out of the 19 organisms isolated, 10 (53%) were Gram-positive cocci, 8 (42%) were Gram-negative rods and 1 (5%) was a fungus. Coagulase negative staphylococci (27%) were the predominant pathogens. Among the staphylococci, 46% of the isolates were methicillin-resistant. All Gram-positive isolates were susceptible to glycopeptides. Gram-negative rods were resistant to most of the commonly used antimicrobial groups. Central venous catheter is an important source of bloodstream infections in cancer patients. Most of the infections are caused by Gram-positive cocci. Rigorous infection control measures and continuous surveillance are required to curb the frequency of these infections.