Post-transplant outcome in chronic myeloid leukaemia.

OBJECTIVE: To determine post-transplant survival in chronic myeloid leukaemia patients undergoing allogeneic stem cell transplant. STUDY DESIGN: Longitudinal, descriptive study. PLACE AND DURATION OF STUDY: Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between April 2002 and August 2007. METHODOLOGY: All patients of chronic myeloid leukaemia in chronic phase having HLA identical donor and age under 55 years, normal hepatic, renal and cardiac functions with good performance status were selected. Patients in accelerated phase or blast crisis, poor performance status, impaired hepatic, renal, cardiac functions or pregnancy were excluded. Survival was calculated from the date of transplant to death or last follow-up according to Kaplan-Meier and Cox (proportional hazard) regression analysis methods. RESULTS: Thirty seven patients with chronic myeloid leukaemia underwent allogeneic stem cell transplant from HLA identical sibling donors. Thirty two patients were male and five were females. Median age of patients was 28 years. All patients and donors were CMV positive. Post-transplant complications encountered were acute GvHD (Grade II-IV) (n=13, 35.1%), chronic GvHD in 18.9% (n=7), Veno Occlusive Disease (VOD) in 5.4% (n=2), acute renal failure in 2.7% (n=1), haemorrhagic cystitis in 2.7% (n=1), bacterial infections in 40.5% (n=15), fungal infections in 16.2% (n=6), CMV infection in 5.4% (n=2), tuberculosis in 5.4% (n=2), Herpes Zoster infection 2.7% (n=1) and relapse in 2.7% (n=1). Mortality was observed in 27% (n=10). Major causes of mortality were GvHD, VOD, septicemia, CMV infection and disseminated Aspergillosis. Overall Disease Free Survival (DFS) was 73% with a median duration of follow-up of 47.4 +/-12 months. DFS was 81% in standard risk and 54.5% in high-risk group. CONCLUSION: Results of allogeneic stem cell transplant in standard risk group CML patients were good and comparable with other international centres, however, results in high-risk CML patients need further improvement, although, number of patients in this group is small.

Pulmonary tuberculosis in allogeneic stem cell transplant recipients.

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.

Management of acute myeloid leukaemia--5 years experience at Armed Forces Bone Marrow Transplant Centre, Rawalpindi.

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.

Successful allogeneic stem cells transplantation in severe aplastic anaemia complicated by dengue Fever.

Aplastic anaemia is characterized by severe compromise of haematopoiesis and hypocellular bone marrow. Haemorrhagic episodes in patients with aplastic anemia occur usually secondary to thrombocytopenia and require frequent support with platelet concentrates and other blood products. Infection with dengue virus (particularly dengue sero type-2 of South Asian genotype) is associated with dengue haemorrhagic fever. Dengue infection further worsens the disease process in patients with aplastic anaemia due to uncontrolled haemorrhagic diathesis and major organ failure, which may prove fatal in these already immunocompromised patients, if not treated in time. Recent epidemics of dengue haemorrhagic fever has not only affected the southern region of our country but also spread to other areas of the country. With this background, we report a case of aplastic anaemia complicated by dengue haemorrhagic fever who achieved successful engraftment after allogeneic stem cell transplantation from sibling brother and is having normal healthy post transplant life.

Deep vein thrombosis--a rare post transplant complication.

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.

Cardiac complications after stem cell transplantation.

Cardiac insufficiency / toxicity has been recognized as a complication of intensive cytotoxic therapy used in stem cell transplant setting. The incidence of clinically significant cardiac toxicity following high dose chemotherapy ranges between 2 - 43% with mortality of 2 - 9%. Two patients are reported who developed life-threatening cardiac complications following cyclophosphamide and busulphan therapy requiring pericardiocentesis and pericardiectomy.

Cutaneous aspergillosis as a first manifestation of systemic infection in allogeneic haematopoietic stem cell transplantation.

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.

Cyclosporine induced neurotoxicity in a stem cell transplant recipient.

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.

Pneumocystis carinii and Trichosporon beigelii pneumonia following allogeneic haemopoeitic stem cell transplantation.

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.

Allogeneic stem cell transplantation in chronic myeloid leukaemia--2 1/2 year experience.

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.