Immunoglobulin heavy chain gene rearrangement in non B-cell haematological malignancies / Reordenamiento del gen de la cadena pesada de inmunoglobulina en las neoplasias hematológicas de linfocitos no B

PURPOSE: Clonality detection through amplifying immunoglobulin heavy chain (IGH) gene rearrangements by polymerase chain reaction (PCR) is a useful tool in diagnosis of various B-lymphoid malignancies. Immunoglobulin heavy chain gene rearrangement can be an optimal target for clonality detection in B-lymphoid malignancies. In the present study, we evaluated the presence of IGH gene rearrangement in non B-cell haemato-oncologypatients including T-cell acute lymphoblastic leukaemia (T-ALL), acute myeloblastic leukaemia (AML) and biphenotypic leukaemia. METHODS: We studied 18 cases of haematological malignancies which comprised five patients with TALL, 12 patients with AML and one with biphenotypic leukaemia. RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement. CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.

OBJETIVO: La detección de la clonalidad mediante amplificación de los reordenamientos del gen de la cadena pesada (IGH) de inmunoglobulina por reacción en cadena de la polimerasa (RCP) es una herramienta útil en el diagnóstico de varios tumores malignos linfoides de células B. El reordenamiento del gen de la cadena pesada de inmunoglobulina puede ser un objetivo óptimo de la detección de la clonalidad en tumores malignos linfoides de células B. En el presente estudio, se evaluó la presencia de reordenamiento del gen IGH en pacientes de hemato-oncología de células no B, incluyendo la leucemia linfoblástica aguda de células T (LLA-T), leucemia mieloblástica aguda (LMA), y leucemia bifenotípica. MÉTODOS: Se estudiaron 18 casos de neoplasias malignas hematológicas que abarcaron cinco pacientes con (LLA-T), 12pacientes con AML y uno con leucemia bifenotípica. CONCLUSIÓN: Reordenamiento del gen de la inmunoglobulina que ocurre en casi todas las neoplasias malignas hematológicas del linaje de las células B, también se presenta en una proporción muy pequeña de células T o las neoplasias mieloides.

Immunoglobulin Heavy Chain Gene Rearrangement in Non B-cell Haematological Malignancies.

OBJECTIVE: Clonality detection through amplifying immunoglobulin heavy chain (IGH) gene rearrangements by polymerase chain reaction (PCR) is a useful tool in diagnosis of various B-lymphoid malignancies. Immunoglobulin heavy chain gene rearrangement can be an optimal target for clonality detection in B-lymphoid malignancies. In the present study, we evaluated the presence of IGH gene rearrangement in non B-cell haemato-oncology patients including T-cell acute lymphoblastic leukaemia (T-ALL), acute myeloblastic leukaemia (AML) and biphenotypic leukaemia. MEHTODS: We studied 18 cases of haematological malignancies which comprised five patients with T-ALL, 12 patients with AML and one with biphenotypic leukaemia. RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement. CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.

Detection of common deletional alpha-thalassemia spectrum by molecular technique in kelantan, northeastern malaysia.

Thalassemia is a hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin polypeptide chains. Although thalassemia mostly affects developing countries, there is limited knowledge of its accurate frequency and distribution in these regions. Knowing the prevalence of thalassemia and the frequency of responsible mutations is therefore an important step in the prevention and control program as well as treatment strategies. This study was performed to determine the prevalence and to study the spectrum of gene deletions that are responsible in α-thalassemia in Kelantan, located in northeastern Malaysia. A total 400 first-time blood donors from multiple areas of donation centre were chosen randomly. The presence of three types of α-thalassemia gene deletion in southeast Asian population which were -(SEA)deletion, -α(3.7) rightward deletion, and -α(4.2) leftward deletion was detected by using multiplex PCR method. 37 (9.25%) of blood donors were confirmed to have α-thalassemia deletion types. 34 (8%) were heterozygous for α3.7 deletion, 1 (0.25%) was heterozygous for α4.2 deletion, and 2 (0.5%) were heterozygous for SEA type deletion. Alpha-thalassemia-2 with 3.7 deletion was the most common determinant detected in Kelantan Malay compared to other ethnic groups. It has been noted that alpha-thalassemia-2 with 3.7 deletion is the most common type of α-thalassemia throughout the world.

Hematological reference values of healthy Malaysian population.

Health and disease can only be distinguished by accurate and reliable reference values of a particular laboratory test. It is now a proven fact that there is considerable variation in hematology reference intervals depending on the demographic and preanalytical variables. There are evidences that values provided by manufacturers do not have appropriate application for all populations. Moreover, reference ranges provided by different laboratory manuals and books also do not solve this problem. We are presenting here normal reference ranges of Malaysian population. These values were determined by using Sysmex XE-2100 and ACL 9000 hematology and coagulation analyzers. Results from this study showed that there were considerable differences in the reference values from manufacturers, western population or laboratory manuals compared with those from the local population.

Response rate of Malaysian blood donors with reactive screening test to transfusion medicine unit calls.

Blood donors with reactive screening test results are requested to come in for counseling by letter and telephone call. It has been noticed many donors responded to neither the letters nor the telephone calls. We evaluated 589 cases with reactive screening test results (208 positive for hepatitis C, 209 for hepatitis B, 85 for VDRL and 87 for HIV). In the hepatitis C positive group 61 donors (29.3%) did not respond and 4.7% missed their follow-up appointment. Similarly low response rates were noted with the HBV (58.9%) and VDRL (67.1%) positive groups. Among HIV positive donors 46.0% failed to respond to multiple calls. We conclude that blood donors in Malaysia have a poor response to calls from the blood transfusion unit. A review of the effectiveness of the current deferral system and an increased public knowledge of transmissible infectious diseases may encourage blood donors to have a better response rate.

Blood pre-donation deferrals--a teaching hospital experience.

Blood donor selection contributes to the safety of both the donor and the recipient. The objective of this study was to identify the number and causes of blood pre-donation deferrals at the Hospital Universiti Sains Malaysia (HUSM). A retrospective study was carried out to retrieve data regarding deferred blood donors at the HUSM in the year 2006. A total of 4,138 blood donors donated blood at the Transfusion Medicine Unit, of whom 231 were deferred or rejected as donors. The percentage of deferred donors was 5.6%. The main reason for deferral was a low hemoglobin (40.7%), with females constituting the majority of those deferred. This was followed by high blood pressure (29.4%) and male donors were predominant in this group. Medical illness caused 15.6% of donor deferrals. The majority of deferred donors were regular donors (64.1%). We recommend setting new hemoglobin criteria for donor deferral according to the reference range obtained for the particular population. Most of the other deferrals were preventable by proper health care education and awareness.

Red cell autoantibodies among thalassaemia patients in Hospital Universiti Sains Malaysia.

INTRODUCTION: Thalassaemia is one of the major public health problems in Malaysia. Regular monthly blood transfusion remains the main treatment for severe thalassaemia patients. One of the complications of blood transfusion is the formation by the recipients of alloantibodies and autoantibodies against red blood cell (RBC) antigen. The purpose of this study was to determine the prevalence of RBC autoantibodies among multiple-transfused thalassaemic patients in our institution and factors that contribute to its development. METHODS: A prospective study was conducted in Haematology Laboratory, Hospital Universiti Sains Malaysia between January 2004 and December 2004. A total of 63 thalassaemia patients, who received regular blood transfusion were included in this study. Clinical and serological data were collected and analysed prospectively. Blood samples were subjected to standard blood bank procedures for screening of antibodies and their subsequent identification using reagent of Diamed-ID Gel microtyping system. RESULTS: There were 49 (77.8 percent) patients with Hb E/beta-thalassaemia, ten (15.9 percent) beta-thalassaemia major, three (4.7 percent) Hb H Constant Spring and one (1.6 percent) Hb H disease. Only one (1.6 percent) patient had autoantibodies. There were no statistical associations found between the formation of autoantibodies with age at the start of transfusion, number of packed cell transfused and splenectomy. CONCLUSION: Our data showed a low autoimmunisation rate in multiple-transfused thalassaemia patients in our hospital.

Identification of hemoglobin AC heterozygote status in a Malay family: a decision between hemoglobin electrophoresis and high performance liquid chromotography.

Thalassemia is a common public health problem among Malays. Hemoglobin C (Hb C) is a hemoglobin beta variant resulting from a single base mutation at the 6th position of the beta-globin gene leading to the substitution of glycine for glutamic acid. Hb C is commonly detected in West Africans and in African American but has not been reported in Malaysia. It can be falsely diagnosed as HbE trait in the Malaysian Thalassemia Screening Program which utilizes cellulose acetate hemoglobin electrophoresis. This is the first reported case of Hb AC heterozygote status in a Malay family, with unusual splenomegaly in one of the family members.

Trends in hepatitis B virus infection among blood donors in Kelantan, Malaysia: a retrospective study.

The objective of this study was to determine the prevalence and trends in hepatitis B infection among blood donors attending the Transfusion Medicine Unit at the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. A retrospective study was carried out by reviewing the results of HBsAg among blood donors for the years 2000 to 2004. During this period, 44,658 blood donors were studied. We noted that there was a significant difference in the prevalence of hepatitis B infection between regular and first time donors. There was also a decreasing trend noticed in both study groups. The mean prevalence was significantly different between first time (1.83%) and regular donors (0.45%) (p < 0.005). There is a need to improve public awareness programs to lower the incidence of hepatitis B infection in the general population and consequently first time blood donors. Future studies are also required to determine the trends and outcomes of these programs.

The prevalence of human cytomegalovirus seropositivity among blood donors at the Unit of Blood Transfusion Medicine, Hospital Universiti Sains Malaysia.

Human cytomegalovirus (HCMV) is a species-specific DNA virus of the Herpetoviridae family. After a primary infection, HCMV persists in a latent form most probably in bone marrow progenitor cells or in peripheral blood monocytes. The virus can reactivate to result in shedding of the virus leading to virus dissemination and new infections. Immunocompromized patients are the ones most vulnerable to serious diseases occasionally acquired in blood transfusions. In a human population, HCMV seropositivity increases steadily with age to become approximately 100% in adults. This study was performed to detect seropositivity among regular blood donors in The Hospital of the Universiti Sains Malaysia, in the state of Kelantan. Using an enzyme immunoassay, it was found that 97.6% of blood donors were HCMV-positive. HCMV is highly prevalent and may be endemic in Kelantan. Hence, long-term strategies are required for the reduction of disease dissemination, and to prevent the exposure of immunocompromized patients to the virus.

A study of serum ferritin levels among male blood donors in Hospital Universiti sains Malaysia.

Iron deficiency is the commonest cause of anemia worldwide and healthy blood donors are estimated to lose about 236 mg of iron with each donation. The objective of this study was to determine the serum ferritin levels among first time and regular male blood donors, and also to correlate the serum ferritin levels with the number of donations and hemoglobin levels. Hemoglobin levels and serum ferritin were measured in three groups of donors divided into first time donors; (n = 92), donors with 2-4 donations (n = 41), and regular donors (n = 78). The mean hemoglobins in the first time donors, second group and regular blood donor group were 14.95 +/- 1.08, 15.12 +/- 1.44 and 15.56 +/- 1.48, respectively. The serum ferritin level were found to be significantly lower among the regular donors (62.0 +/- 39.78 ng/ml) compared to first time donors (90.7 +/- 66.63) and second group donors (114.12 +/- 66.97). The serum ferritin levels gradually decrease according to the number of donations and there was a significant correlation between frequency of donations and the serum ferritin level (r2 = 0.082). Significant correlation between the number of donations and hemoglobin level r2 = 0.061) was noted. However, there was no significant correlation between hemoglobin and serum ferritin levels (r2 = 0.015). Eleven percent of regular donors had depleted iron stores. This was not noted in donors who donated less than 5 times within 2 years.

Thalassemia among blood donors at the Hospital Universiti Sains Malaysia.

The aim of this study was to screen and identify the types of thalassemia among blood donors at the Hospital Universiti Sains Malaysia (HUSM). Thalassemia screening was performed by hemoglobin electrophoresis. A total number of 80 blood samples were obtained from donors at the Transfusion Medicine Unit, HUSM. The ethnic origins of the donors were Malays (n=73, 91.3%) and non-Malays (n=7, 8.75%). Males comprised 88.1% of the donors. Thalassemia was detected in 16.25% (n=13) of the blood donors. Of those with thalassemia, 46.2% (6/13) were anemic. Microcytosis and hypochromia were detected in 84.6% (n=l1) and 84.6% (n=l1) of these donors, respectively. The types of thalassemias detected were Hb E, 11.25% (n=9/80) and beta thalassemia trait, 5% (n=4/80). Among the thalassemias detected, the Hb E hemoglobinopathy was comprised of Hb E/ alpha-thalassemia (38.5%: n=5), Hb E /beta-thalassemia (23.1%: n=3), Hb E trait (7.6%: n=1) and beta-thalassemia (30.8%: n=4). In conclusion, screening for thalassemia trait should be included as part of a standard blood testing before blood donation. Further studies are required to look at the effects of donated thalassemic blood.

Red cell immunization in multiply transfused Malay thalassemic patients.

The development of red blood cell (RBC) isoimmunization with alloantibodies and autoantibodies complicate transfusion therapy in multiply transfused thalassemia patients. Thus, the frequency, causes and prevention of these phenomena were studied among these patients. Clinical and serological data from 58 Malay multiply transfused thalassemic patients who sought treatment at Hospital University Sains Malaysia were collected and analyzed prospectively. Blood samples were subjected to standard blood bank procedures to screen for antibody and subsequent antibodies identification. All patients in our hospital received blood matched for only ABO and Rh (D) antigens. There were 46 (79.3%) patients with Hb E/beta thalassemia, 8 (13.8%) with beta thalassemia major, 3 (5.2%) with Hb H Constant Spring and 1 (1.7%) with Hb H disease. Overall, 8.6% of the patients had alloantibodies and 1.7% had autoantibodies. The alloantibodies identified were anti-E, anti-c, anti-K, anti-Jka, anti-N and anti-S. In conclusion, the transfusion of matched blood is essential for chronically multiply transfused patients in order to avoid alloimmunization. Considering the high frequency of anti E at our hospital, it is advisable to genotype patients and match the red cells for E antigens in multiply transfused thalassemia patients.

Research on cancer diagnosis in Malaysia: current status.

Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer diagnosis, accounting for 65.6% (RM 9.7 million) of cancer project funds. The 8th Malaysia Plan saw a change in research strategy. The IRPA agency fielded several top-down projects which encouraged a multicentre and multidisciplinary approach. This resulted in larger funding per project i.e. RM32 million for 49 projects. There was also a surge of interest in drug development and natural products. Because of this shift in direction, cancer diagnosis projects constituted only 51% of IRPA-funded cancer projects. Nonetheless funding for cancer diagnosis research has exceeded that of the 7th Malaysia Plan, being RM12.5 million by March 2004. The majority of such research is carried out at the Universities, engaging a large number of young scientists and postgraduate students (51 MSc and 21 PhD). A lot of research findings presented at scientific meetings have not yet been published and there is a glaring shortage of patents and commercialization of research findings (such as creation of test kits). Because diagnosis is very much a part of clinical practice, many researchers felt satisfied and confident that their work will be translated into practice and will significantly improve diagnostic services in Malaysia. National guidelines and consensus development on at least three malignancies i.e. breast cancer, oral cancer and lymphoma, have substantial basis in local R&D work. Problems encountered in research included (1) insufficient funding to realize research objectives, (2) lack of local expertise (most research assistants are inexperienced BSc graduates with no or minimal research experience), (3) inadequate technical support from vendors during equipment failure, (4) inexperienced Institutional development units to assist in product development, (5) lack of venture capital for commercialization of findings, and (6) inadequate incentives to undertake research. Researchers pointed out that plans to promote research should include the establishment of (1) regional and national cancer tissue banks, (2) a National Cancer Research Institute, (3) a dedicated cancer research fund, (4) a registry of cancer researchers, (5) national research coordinators, (6) improved coverage by the National Cancer Registry, (7) more international collaboration, (8) a better career structure for researchers, (9) improved Institutional support for product realization, and (10) better recognition for cancer researchers.