Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.
Nephrotic syndrome (NS) is a well documented complication after allogeneic peripheral blood stem cell transplantation. It is usually due to autoimmune glomerulonephritis and thought to be a clinical manifestation of graft versus host disease. NS has also been reported to be associated with other hematological malignancies. We report a case of nephrotic syndrome in a patient who relapsed after allogeneic peripheral blood stem cell transplantation (PBSCT) for chronic myeloid leukemia (CML). The renal biopsy was suggestive of minimal change disease. There was no other evidence of graft versus host disease. He was treated with high dose prednisolone, with no response and finally succumbed to the underlying disease.
This study was done to assess the overall response rate of imatinib mesylate in local patients with chronic myeloid leukaemia. A total of 69 patients were recruited with male/female ratio of 7:3. Of the 69 patients; 35% were in the chronic phase, 41% were in the accelerated phase, 17% were in blast crisis and the remaining 7% were after stem cell transplantation. Complete haematological response rates of patients in chronic phase, accelerated phase and blast crisis were 95.8%, 96.4% and 41.7% respectively. Thirty-eight percent of patients achieved complete cytogenetic response and 10% achieved partial cytogenetic response. The cytogenetic response rates were 80%, 41.7% and 18.2% in chronic, accelerated and blast crisis phase respectively (p < 0.005). Twenty-six percent of patients developed anaemia, 13% had neutropenia and 12% had thrombocytopenia after starting on treatment. In addition, 14% of patients developed peripheral oedema, 13% complained of musculoskeletal pain, 12% had gastrointestinal side effects which include nausea, vomiting and diarrhoea, 9% had grade 1 hepatotoxicity, 7% developed skin rashes and one patient had an abnormal renal function test. Patients taking 600mg or higher dosage of imatinib had more gastrointestinal side effects. Patients who weighed less than 60kg had a much higher risk of developing anaemia. Anaemia was a negative predictor of cytogenetic response. Presenting high white blood cell counts and absence of cytogenetic response were also negative predictors of survival. Overall survival was 87%. This was affected by the different phases of disease (chronic phase was better than accelerated and blast crisis) (p < 0.001). In conclusion, our local CML patients did well on treatment with imatinib.
We report a case of a child with severe congenital neutropenia (Kostmann's syndrome) who was treated with daily prophylactic subcutaneous granulocyte colony-stimulating factor (G-CSF) from the age of eight to sixteen years before being discontinued for poor haematological and clinical response. She did not have a HLA-matched sibling to enable bone marrow transplantation. She subsequently developed acute megakaryoblastic leukemia at the age of 17 years and succumbed during induction chemotherapy. The role of G-CSF in the pathogenesis of her malignant transformation to AML is complicated as this disorder has a propensity for myelodysplasia or AML as part of its natural history.
Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage.
Chronic Myeloid Leukaemia (CML) is a disease characterised by a distinctive marker that is the Philadelphia Chromosome and an ability to transform into blast phase, which confers a poor prognosis. The median survival was reported to be between three to six months in correlation to blast phase. Extramedullary involvement with CML to sites such as pleural, meningeal and bones have been reported. We report a case of 41-year-old man who was diagnosed with CML in blast phase and presented with ascites. Ultrasound of abdomen showed coarse echotexture of liver suggestive leukaemic infiltration to the liver. The liver profile was severely deranged and associated with coagulopathy. Flow cytometry analysis of the peritoneal fluid revealed presence of myeloblasts consistent with CML in blast crisis with leukaemic ascites. Bone marrow biopsy also confirmed disease transformation. He received standard induction chemotherapy for acute myeloid leukaemia with dose modifications based on liver enzymes performance. Our case highlights an unusual presentation of CML in blast crisis with leukaemic ascites and the challenges in managing cytotoxic treatments due to the liver infiltration.
Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus. APL is unique because it is usually associated with a coagulopathy that markedly increases the risk for the mother and fetus. A 21 year old lady with APL in her third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed the coagulopathy and normalised her blood counts without causing cytotoxic damage associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of gestation and an emergency caesarean section was performed without complications and no blood transfusion support was needed as her coagulopathy and thrombocytopenia had resolved. A remission was achieved with only tretinoin induction. She subsequently had consolidation and maintenance chemotherapy. The mother and baby remain well at 4 years from completion of chemotherapy. A total of 10 pregnancies associated with APL have been reported in the current literature. Premature delivery and a fetal arrhythmia were the only complications. Although retinoin is considered teratogenic, its use so far in second and third trimester has been safe.
Acute leukaemia may rarely present as diffuse papules, nodules and plaques forming leonine facies. Leukaemia cutis generally carries a poor prognosis, and responds less well to chemotherapy. We described a case of acute myelomonocytic leukaemia presenting as leonine facies as a result of extensive cutaneous infiltration. The patient did not achieve haematological remission following standard induction chemotherapy and succumbed 6 weeks after the diagnosis was made.
The effect of L-asparaginase on the thyroid gland has not been well documented. We report the first two cases of hyperthyroidism associated with thyroid nodule following L-asparaginase therapy for acute lymphoblastic leukemia (ALL). The thyroid function abnormalities were not severe, short-lived and did not require specific therapy.
Second malignant neoplasms (SMN) are an increasingly recognized late complication seen in childhood cancer survivors. A total of 3 cases of SMN have been found in the Department of Paediatrics, University Hospital Kuala Lumpur after a 15-year experience of treating childhood malignancies. Two cases are described here. The first developed abdominal non-Hodgkin's lymphoma 3 years after undergoing an allogeneic bone marrow transplant for second relapse of acute lymphoblastic leukaemia, while the second child developed myeloid leukaemia two years after completing treatment for acute lymphoblastic leukaemia. Progress in the management of childhood cancer in Malaysia and the availability of bone marrow transplantation facilities have increased the number of childhood cancer survivors; leading to increased incidence of SMN.
A six year old Chinese boy with relapsed Acute Promyelocytic Leukaemia (APML) failed to respond to reinduction with Daunorubicin and Cytarabine infusion. He was successfully treated with all trans-Retinoic Acid (45 mg/m2/day) orally. After four weeks of treatment, he was in complete remission. The side effects of all trans-Retinoic Acid were negligible.
Two 4-year-old monozygotic Chinese, female twins developed concordant childhood acute lymphoblastic leukemia (ALL) within an interval of about 2 weeks. Based on morphology and cytochemistry findings of the bone marrow blast cells, a diagnosis of ALL, L1 was made. Immunophenotyping showed the blast cells of both twins expressed similar antigens, i.e. HLA-DR, CD10, CD13, CD19, CD22 and CD34. Identical blood group, same HLA (human leucocyte antigen) genotype, sex and similar appearance suggest that the twins are monozygotic. Since the bone marrow leukemic cells of both twins were identical in morphology and expressed the same antigens with almost similar percentages of positivity, it is likely that the blast cells were derived from the same single clone. Based on the single clone hypothesis, the leukemogenic event must have arisen in utero in one twin and the cells from the abnormal clone then spread to the other twin via shared placental anastomoses.
The variant form of acute promyelocytic leukaemia (AML-M3) possesses its own characteristic morphology, although usually a few of the cells may have cytoplasmic features of typical AML-M3. In contrast to typical AML-M3, this M3-variant form commonly presents with hyperleucocytosis. As in typical AML-M3, disseminated intravascular coagulopathy (DIVC) occurs in the M3-variant. A boy with this morphological variant of AML-M3 is described. Uncharacteristically, his presenting white blood count was low, and DIVC was present before treatment was started. Six days into intensive chemotherapy his coagulopathy worsened and he subsequently died of intracranial haemorrhage. An alternative approach to the treatment of AML-M3, with the use of retinoids, is discussed.
A six-year-old boy, a known case of acute lymphoblastic leukaemia (ALL) on remission since 1991 presented with leukocoria and poor vision of the left eye for two days' duration. Examination revealed endophthalmitis in the left eye with raised intraocular pressure. Anterior chamber paracentesis with vitreous biopsy confirmed a diagnosis of ocular involvement. Further investigation revealed that he also had bone marrow and central nervous system relapse. Clinical manifestation and treatment modalities of ocular involvement in leukaemia are discussed.
Intensive chemotherapy has prolonged survival in cancer patients. Unfortunately it has also predisposed them to unusual infections because of their immunocompromised state. We report a case of fungal septicaemia caused by Geotrichum candidum, an imperfect yeast of low virulence in a young girl with acute lymphoblastic leukaemia. It was successfully treated with amphotericin B. The morphological characteristics of this fungus leading to its identification are described.
Primary varicella-zoster virus infection in children with haematological malignancy is a life threatening disease. In one year, there were 10 cases of varicella and 2 cases of zoster among these children as well as 5 mothers who were accompanying their children who developed varicella in the oncology ward. Two children died of fulminating disease despite aggressive antiviral and supportive treatment. Acyclovir can be used in treatment and prophylaxis in exposed susceptible children. Varicella -zoster immune globulin is not available in this country. Vaccination with live virus has been shown to be protective in immunocompromised children and needs consideration.
Deoxyribonucleic acid (DNA) of twenty chronic myeloid leukemia (CML) and thirty acute lymphoblastic leukemia (ALL) patients were analysed by Southern hybridization. The DNA was digested with BglII and hybridized with a 4.5-kilobase (kb) ph1/bcr-3 DNA probe. All the 20 CML patients showed gene rearrangement within a 5.8-kb segment (the major breakpoint cluster region, M-bcr) of the breakpoint cluster region (bcr) gene of chromosome 22, indicating the presence of the Philadelphia chromosome. M-bcr rearrangement at the bcr gene of chromosome twenty-two was not detected in all the thirty ALL patients (nine adults and twenty-one children) and two normal controls.
Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.
Congenital leukaemia which is characterised by proliferation and extrahaemopoietic infiltration of immature leucocyte precursor cells is a rare disorder encountered in the neonatal period. Although more than 100 cases of congenital leukaemia have been reported in the literature, the experience of most general paediatricians with this condition is very likely to be limited. Thus a patient presenting with congenital leukaemia admitted to Alor Star General Hospital is reported.