A young patient presenting with splenomegaly and hypersplenism was inadvertently found to have selective IgA deficiency. There were no symptoms of immunodeficiency and the patient responded well to splenectomy, with return of blood counts to normal without adverse effects. No other cause for the hypersplenism was found. We postulate selective IgA deficiency as a cause of splenomegaly and hypersplenism.
Forty-six Malaysian patients with chronic granulocytic leukaemia were found to be rearranged in the breakpoint cluster region (BCR) of chromosome 22, molecular evidence of Philadelphia chromosome (t9.22) translocation. Through the use of a 1.2 kb 3' BCR probe and two restriction enzyme digests, patients' breakpoints could be localized either to 5' or 3' regions of the BCR. Breakpoint site localization at the time of DNA sampling did not show any positive statistical association to clinical status defined as chronic phase, chronic phase with less than 6 months to blast crisis, accelerated phase and blast crisis. This was in contrast to earlier reports which indicated that patients with breakpoint at 3' site were at a higher biologic risk for entering blast crisis.
Rearrangements in the DNA of chronic myelogenous leukemia patients of Chinese, Malay and Indian origin were detected in the breakpoint cluster region of chromosome 22 using molecular techniques. The DNA of fifty patients was examined using a 1.2 kb DNA probe. Rearrangements were detected in 46/50 patients. Karyotypic data were available in nine patients, all of whom were Philadelphia chromosome positive and exhibited DNA rearrangement. Detection of the Philadelphia translocation by molecular methods, at this institution, where cytogenetics is not routinely performed, confirms its diagnostic value. The rearrangement data obtained in this study is consistent with molecular features of chronic myelogenous leukemia patients of Western countries.
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.
Ninety-two women with systemic lupus erythematosus treated with oral cyclophosphamide were studied to ascertain the prevalence and the factors associated with ovarian dysfunction. Menstrual disturbance during treatment occurred in 55% of patients: 36% had amenorrhoea and 19% had oligomenorrhoea. Sustained oligomenorrhoea occurred in 12% patients. Permanent amenorrhoea (> 12 months) after cessation of oral cyclophosphamide occurred in 27% of patients. Hormonal studies in these patients were consistent with ovarian failure. Older age at initiation of treatment and high cumulative dose of cyclophosphamide were found to be associated with this outcome. There was a trend towards linear relationship between the age of initiation of cyclophosphamide therapy and frequency of amenorrhoea. A statistically significant association between amenorrhoea and cumulative dose of cyclophosphamide after adjustment for age was found whereas no such association was linked to the duration of treatment. Fourteen of the 23 women who wished to become pregnant after cessation of treatment conceived resulting in 20 live births and two abortions.
Pregnancy following idiopathic aplastic anaemia is rare and is difficult to manage because of life-threatening episodes of bleeding and infections. Only a handful of cases has been reported in the literature. The pregnancies were unsuccessful in the majority. The present report describes a patient with moderately severe idiopathic aplastic anaemia who was managed with intensive haematological support leading to delivery of a healthy infant by caesarean section. Despite platelet transfusion refractoriness as a result of transfusions prior to pregnancy, adequate platelet transfusions prevented excessive bleeding. The literature is reviewed and management with platelet transfusions is discussed.
Acute aortic thrombosis is a rare condition, occurring mainly as a result of trauma or atherosclerosis and occasionally secondary to hypercoagulable states. We report a patient with relapsed acute myeloid leukaemia who developed an unusual complication, acute aortic thrombosis.
Induction of remission of acute promyelocytic leukaemia (APL) needs intensive blood support (16) to prevent bleeding attributed to disseminated intravascular coagulation. Between 1989 and 1991, at the University Hospital in Kuala Lumpur, Malaysia, the remission rate of APL was only 27% with conventional chemotherapy as a result of inadequate transfusion resources. The use of all trans retinoic acid in induction therapy followed by consolidation and maintenance chemotherapy has improved the situation dramatically. Twelve patients entered the study. Ten patients achieved remission (83%), indicating how ATRA had significantly improved the results (p = 0.003). Blood component transfusions were also significantly reduced (p = 0.003). Two ethnic Chinese patients developed pulmonary leucostasis. Published Chinese (2, 6) and Japanese (11) studies have not reported this serious adverse effect. We can now state that leucostasis is not a phenomenon limited to the Western population. ATRA has proved to be extremely beneficial for patients at this centre. Early analysis also suggests that consolidation and maintenance chemotherapy has prolonged remission duration. ATRA should be made available for the treatment of APL in all countries where there are inadequate transfusion services.
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.
In vitro deoxyribonucleic acid (DNA) amplification by the polymerase chain reaction (PCR) followed by hybridization with oligonucleotide probes were used to study ras gene mutations in acute myeloid leukemia (AML). The DNA of 30 AML patients at presentation of the disease at the University of Malaya Hospital, Kuala Lumpur were screened for ras gene mutations in codons 12, 13 and 61 of the N-ras, K-ras and H-ras genes. Four patients (13.3%) had ras gene mutations. They were all below their early thirties in age. Of the four patients with ras gene mutations, three were M3 and one was M4 according to the French American British (FAB) classification of AML.
SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.
Antilymphocyte globulin (ALG) was given every other day for 5 doses with platelet transfusions immediately following ALG administration in 6 patients with aplastic anaemia. Four patients responded and 3 durable remissions were achieved. One patient relapsed and further treatment with anti-thymocyte globulin and cyclosporin also failed. One patient died of Flavobacterium septicaemia 6 days after completion of ALG. Our data suggests that using an alternate day regimen, a response rate similar to a daily regimen can be obtained.
Acquired haemophilia is a rare clinical condition arising from the spontaneous development of inhibitors to factor VIII. We describe two cases encountered in the University Hospital over the past five years. We also review the literature and discuss the therapeutic difficulties faced in dealing with patients with high levels of inhibitors. In one of these patients we also describe, for the first time in this region, a novel method in managing the acute bleeding episode in acquired haemophilia using recombinant factor VIIa.
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.
The neutrophil antigen (NA)1 and 2 is coded by two recognized allelic forms of Fc gamma receptor IIIB (FcgammaRIIIB). FcgammaRIIIb is a low affinity receptor and preferentially removes immune complexes from the circulation. Systemic lupus erythematosus (SLE) is an autoimmune and polygenic disorder characterized by accumulation of autoimmune complexes. The majority of SLE patients in our medical center are of Chinese ethnicity, followed by Malay and Indian. Recently, studies have focussed on the Fc receptors in different ethnic groups and their relation to SLE. We chose to study the gene distribution of this receptor in the Chinese and Malays population in Malaysia. We designed a polymerase chain reaction allele specific primers (PCR-ASP) method to distinguish the two allelic forms. Genomic DNA was isolated from the peripheral blood of 183 Chinese and 55 Malays SLE patients as well as 100 Chinese and 50 Malays healthy controls. Genotyping of Chinese SLE patients revealed that the gene frequencies for FcgammaRIIIB-NA1 and FcgammaRIIIB-NA2 were 0.648 and 0.347, while in the ethnically matched healthy controls they were 0.68 and 0.32, respectively. One out of the 183 Chinese SLE patients was identified as a NA-null due to the absence of PCR product for both alleles. The FcgammaRIIIB-NA1 and FcgammaRIIIB-NA2 allele frequencies for both the Malays SLE and healthy controls were 0.62 and 0.38.
An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators. The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia. The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively. This did not differ significantly from the respective healthy groups (20 and 29%). The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status.