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Objective: To highlight the association of early donor chimerism status at 2nd month with various survival outcomes., Method: The retrospective study was conducted at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, and comprised patient data from January 2011 to July 2016. Data related to participants who underwent human leukocyte antigen-matched transplants for bone marrow failure syndrome and beta thalassemia major. Short tandem repeat-based polymerase chain reaction was used to assess donor chimerism status. Overall survival, disease-free survival, relapse-free survival, and graft versus host disease-free survival rates were noted. Data was analysed using SPSS 23., Results: Of the 106, 64(60.4%) had bone marrow failure syndrome and 42(39.6%) had beta thalassemia major. The overall median follow-up was 13.53 months (range: 1.81-62.73 months). Early donor chimerism status was associated with overall survival (p=0.02) and disease-free survival (p=0.01). Mixed donor chimerism was less hazardous in terms of overall survival (p=0.04) and disease-free survival (p=0.02)., Conclusions: Early mixed donor chimerism contributed to optimal survival in nonmalignant disease.

Neurological complications are quite frequent in stem cell transplant (SCT) recipients. Major causes are conditioning regimen toxicity, metabolic and electrolyte disturbances, viral infections and cyclosporine related toxicity. Cyclosporine induced neurotoxicity is a well documented complication in stem cell transplant recipients. These patients usually present with seizures which are easily controlled with anti-convulsants and by reducing/withholding the drug. However uncontrolled seizures requiring ventilatory support are rarely reported. Here we present a case report of cyclosporine induced uncontrolled seizures in a young female after allogeneic SCT which was unresponsive to anti-convulsive therapy but was successfully treated with mechanical ventilatory support.

Mycobacterium tuberculosis is a serious, but rare infectious complication after allogeneic bone marrow transplantation. Tuberculosis is a major problem in South East Asia, particularly in India and Pakistan. We describe here infection due to mycobacterium tuberculosis in four patients after allogeneic stem cell transplantation (Allo SCT). The diagnosis was made on the bases of clinical findings, sputum / blood / pleural and pericardial fluids / broncho alveolar lavage (BAL) and tissue biopsy examination. Anti tuberculosis therapy (ATT) was started immediately after diagnosis. Three patients responded to antituberculosis therapy, where as one patient developed severe infective respiratory complications and died at six months post transplant. Mycobacterial infection should be considered in patients post allo SCT with unexplained fever, cough or pleuritic chest pain. These patients at diagnosis should be promptly treated with ATT.

Deep vein thrombosis (DVT) is a rare post transplant multifactorial disease and often results from a combination of risk factors causing venous stasis. Venography and doppler ultrasound are reliable and accurate procedures for detecting venous thrombosis. Once DVT has been established, these patients should be treated with anticoagulants at least for a limited duration particularly in high risk post transplant patients with previous episodes of thrombotic events. We report here a case of a 7 years old boy with B-thalassaemia major, who developed deep vein thrombosis at 04 month post SCT. He was treated with low molecular weight heparin and oral warfarin sodium and INR was stabilized between 2.5 - 3.0. Two months later, he presented with bleeding diathesis and died intracranial haemorrhage. Excessive unchecked anticoagulation was the cause of death. It is recommended that patients on anticoagulation therapy require strict monitoring with PT/INR to avoid bleeding complications related to unchecked over anticoagulation.

Objective: To evaluate the outcome in denovo AML patients treated with different remission induction and consolidation chemotherapy regimens in our population., Methods: A retrospective study on acute myeloid leukaemia (AML) patients was carried out at Armed Forces Bone Marrow Transplant Centre Rawalpindi Pakistan between July 2001 and June 2006. During 5 years period 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.

Infections are one of the major causes of morbidity and mortality after stem cell transplantation (SCT). Opportunistic infections of varying severity with bacterial fungal and viral organisms occur in > 90% of patients after allogeneic SCT. Fatal opportunistic infections have been reported in 4-15% of related transplant recipients and 12-28% of unrelated transplant recipients. More than half of the transplant patients affected by invasive aspergillosis die despite treatment. Cutaneous aspergillosis has been rarely reported in transplant patients. During last five years 154 patients underwent allo SCT at our centre for various haematological disorders. Aspergillus infection was observed in six patients. Three patients had systemic aspergillosis whereas other three patients had primary cutaneous aspergillus infection. Patients with primary cutaneous aspergillosis are presented here as case report.

Pneumocystis Carinii and Trichosporon beigelii are opportunistic infections in immunocompromised patients. We report a case of a young lady who underwent haemopoeitic stem cell transplantation for relapsed acute lymphoblastic leukemia. This 25 years old female developed fever, dry cough and rapidly progressive dyspnoea during post transplant neutropenia and was found to be suffering from Pneumocystis carinii pneumonia. She was successfully treated with Co-trimoxazole. The patient again presented with similar symptoms on day 55 post transplant. This time Trichosporon beigelii was isolated from bronchoalveolar lavage and she responded to prompt antifungal therapy. Other complications encountered during the subsequent course were extensive subcutaneous emphysema and spontaneous pneumothorax that required chest intubation and brief hospitalization. The patient is presently nine months post transplant and is asymptomatic.

Objective: To study the epidemiology and status of resistance to antimonial compounds of paediatric hospital population with visceral leishmaniasis in Muzaffarabad, Azad Jammu and Kashmir, Pakistan., Methods: Children admitted between January to December 1999 in Azad Kashmir Combined Military Hospital Muzaffarabad and diagnosed as Visceral Leishmaniasis by demonstration of Leishmania parasites in bone marrow aspirate were included in the study. Patients received meglumine antimoniate for 21 days. The demographic information and time taken for resolution of fever after initiation of treatment were recorded., Results: During study period out of 3520 paediatric admissions, 61 patients had visceral leishmaniasis. The frequency of disease was 1.73%. Median age of the patients was 18 months. Eighty two percent cases reported during non-winter seasons. Fifty nine (96.7%) patients responded to treatment with antimonial compounds. Median time taken for resolution of fever was 5.7 days. Two of the patients died during the study period., Conclusion: Childhood visceral leishmaniasis is common in Muzaffarabad and there is no resistance to antimonial compounds.

Objective: To evaluate out come of allogeneic Stem Cell Transplantation (SCT) in chronic myeloid leukaemia (CMC) at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from April 2002 to October 2004., Methods: Twenty-two patients with CML underwent allogeneic SCT from HLA matched siblings. Patients were divided into standard (n=14) and high-risk (n=8) groups. Patients were subjected to conditioning regimens consisting of Busulphan and Cyclophosphamide. Cyclosporin, Prednisolone and Methotrexate were given for GvHD prophylaxis. All donors were subjected to PBSC harvest after G-CSF therapy for five days. All received G-CSF from Day+5 until ANC >0.5 x 10(9)/l., Results: The median age of the patients was 29 years (range 7-53 years) with a male to female ratio of 6.3:1. Engraftment was achieved in all patients. Median time to achieve neutrophil (ANC 0.5 x 10(9)/l) and platelet (20 x 10(9)/l) recovery was 13 days and 12 days respectively. Median stay in hospital was 18 days. Acute GvHD (Grade-II-IV) was observed in eleven patients (50%) while chronic GvHD was seen in four patients (18%). One patient relapsed 8 months post transplant. Two patients (9%) developed Veno-occlusive disease (VOD) liver. One patient had haemorrhagic cystitis. Four patients (18%) had post transplant infectious complications, which included pseudomonas septicemia, aspergillosis, tuberculous pleural effusion and herpes zoster. Overall mortality was 22.7% (n=5). The major causes of mortality were VOD liver, GvHD grade IV, Pseudomonas septicaemia and aspergillosis. Overall survival was 77.2% (n=17) and disease free survival was (n=16) 72.7%. Follow up ranges were from 23 to 828 days (median 212 days)., Conclusion: The preliminary results of SCT in this small series of patients with CML are very encouraging. To improve the long-term survival it is imperative that patients are transplanted early after diagnosis and conditioning regimens are selected carefully.

Objective: To evaluate the frequency and outcome of graft versus host disease after allogeneic stem cell transplant in haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004., Methods: Eighty-six patients with various haematological disorders namely aplastic anaemia (n=32), b-Thalassaemia (n=25), CML (n=22), ALL (n=3), AML (n=1) Fanconi's anaemia (n=2), and Gaucher's disease (n=1), underwent allogeneic stem cell transplantation. All patients received cyclosoprin, prednisolone and short course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD > grade-II or chronic extensive GvHD received steroids at a starting dose of 2 mg/kg body weight along with gradual increase in cyclosporine dosage (max dose 12.5 mg/kg)., Results: The overall incidence of acute GvHD grade-II to IV was 44.2% (n=38/86) where as the incidence of chronic extensive GvHD was 14% (n=12/86). Acute GvHD was 68% (n=17/25) in beta-Thalassaemia, 50% (n=11/22) in CML, 50% (n=2/4) in Acute Leukaemias and 25% (n=8/32) in Aplastic Anaemia. Chronic GvHD was 25% (n=1/4) in Acute Leukaemias, 18.8% (n=6/32) in Aplastic Anaemia, 18.2% (n=4/22) in CML and 4% (n=1/25) in beta-Thalassaemia. The overall survival in acute GvHD was 84.2% (n=32) where as the overall survival in chronic GvHD was 50% (n=6). The overall mortality in acute GvHD was 15.8% (n=6) and 50% in chronic GvHD (n=6)., Conclusion: The morbidity and mortality due to severe acute and chronic GvHD remains high despite standard prophylaxis against GvHD. New strategies are needed to prevent and treat GvHD.

Objective: To evaluate the role of isoniazid prophylaxis in prevention of tuberculosis among allogeneic stem cell transplant recipients., Methods: This study was conducted at Armed Forces Bone Marrow Transplant Center Rawalpindi, Pakistan from July 2001 to October 2003. Patients suffering from various haematological disorders undergoing allogeneic stem cell transplantation were included in the study. The demographic information, primary diagnoses and relevant investigations were recorded. Patients had negative tuberculin skin tests and chest X-Ray at pre-transplant assessment. First 25 patients (group I) did not receive isoniazid prophylaxis while the next 25 (group II) were given isoniazid in a dose of 5-10 mg/kg (maximum 300 mg/day). Isoniazid prophylaxis was started on day-1 and continued for 6 months post transplant. The patients developing tuberculosis were treated with rifampicin, ethambutol, isoniazid, and pyrazinamide during first 3 months followed by 2 drugs for a total duration of 12 months. Minimum follow up in group I and II was 783 and 403 days respectively., Results: There was significant difference (p < 0.001) in frequency of tuberculosis between two groups. In group I, four patients developed Tuberculosis (frequency 16%) whereas none of the patients in group II had the disease. Out of these four cases 3 had extrapulmonary disease. One patient died two weeks after the start of anti tuberculosis treatment while others successfully completed the treatment., Conclusion: Tuberculosis in stem cell transplant recipients is an important opportunistic infection especially in areas of high disease prevalence like Pakistan. Isoniazid prophylaxis for 6 months is effective in preventing tuberculosis among this class of patients.

Objective: To evaluate the efficacy and toxicity profile of the combination of fludarabine, high dose cytarabine, idarubicin, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a study is being conducted at Armed Forces Bone Marrow Transplant Centre (AFBMTC) Rawalpindi since January 2003. Data up to June 2004 (early report) is being presented., Methods: Twelve Patients with refractory/relapsed (Ref/Rel) acute leukaemia (AL) were treated with fludarabine 30 mg/m2 and cytosine arabinoside (AraC) Arac 2 g/m2 for 5 days, idarubicin 10 mg/m2 for 3 days, and granulocyte colony stimulating factor G-CSF 5 micro g/kg from day 0 till neutrophil recovery (ANC > 1.0 x 10(9)/1). Response was evaluated by bone marrow examination on day 20-post chemotherapy., Results: Patients included were refractory acute lymphoblastic leukaemia (ALL) (n=2), relapsed ALL (n = 3), refractory acute myeloid leukaemia (AML) (n = 3), secondary AML (n=2) relapsed AML (n = 1) and acute undifferentiated leukaemia (AUL) (n = 1). Complete remission (CR) was achieved in 8 (66.6%) patients. Three (25%) patients died of post chemotherapy complications and one patient failed to achieve remission. Out of 8 patients who achieved CR, 4 underwent allogeneic bone marrow transfusion (BMT), 1 is being evaluated for the same, 1 received idorubicin, AraC and etopuside (ICE) and high dose AraC, 1 did not receive further chemotherapy and 1 relapsed two months after remission. Seven patients are still in CR after a median follow up of 8 months (range 3-18). Major complications encountered were diarrhoea, mucositis, toxic ileus, transient hepatic toxicity, fungal and bacterial infections., Conclusion: In our experience, FLAG-IDA is well tolerated and effective regimen in relapsed/refractory acute leukaemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.