Advancements in HLA Typing Techniques and Their Impact on Transplantation Medicine.

HLA typing serves as a standard practice in hematopoietic stem cell transplantation to ensure compatibility between donors and recipients, preventing the occurrence of allograft rejection and graft-versus-host disease. Conventional laboratory methods that have been widely employed in the past few years, including sequence-specific primer PCR and sequencing-based typing (SBT), currently face the risk of becoming obsolete. This risk stems not only from the extensive diversity within HLA genes but also from the rapid advancement of next-generation sequencing and third-generation sequencing technologies. Third-generation sequencing systems like single-molecule real-time (SMRT) sequencing and Oxford Nanopore (ONT) sequencing have the capability to analyze long-read sequences that span entire intronic-exonic regions of HLA genes, effectively addressing challenges related to HLA ambiguity and the phasing of multiple short-read fragments. The growing dominance of these advanced sequencers in HLA typing is expected to solidify further through ongoing refinements, cost reduction, and error rate minimization. This review focuses on hematopoietic stem cell transplantation (HSCT) and explores prospective advancements and application of HLA DNA typing techniques. It explores how the adoption of third-generation sequencing technologies can revolutionize the field by offering improved accuracy, reduced ambiguity, and enhanced assessment of compatibility in HSCT. Embracing these cutting-edge technologies is essential to advancing the success rates and outcomes of hematopoietic stem cell transplantation. This review underscores the importance of staying at the forefront of HLA typing techniques to ensure the best possible outcomes for patients undergoing HSCT.

KIR genotype and haplotype repertoire in Kuwaiti healthy donors, hematopoietic cell transplant recipients and healthy family members.

The gene complex located on chromosome 19q13.4 encodes the Killer-cell Immunoglobulin-like Receptors (KIRs), which exhibit remarkable polymorphism in both gene content and sequences. Further, the repertoire of KIR genes varies within and between populations, creating a diverse pool of KIR genotypes. This study was carried out to characterize KIR genotypes and haplotypes among 379 Arab Kuwaiti individuals including 60 subjects from 20 trio families, 49 hematopoietic cell transplantation (HCT) recipients and 270 healthy Kuwaiti volunteer HCT donors. KIR Genotyping was performed by a combination of reverse sequence specific oligonucleotide probes (rSSO) and/or Real Time PCR. The frequencies of KIR genes in 270 healthy Kuwaiti volunteer donors were compared to previously reported frequencies in other populations. In addition, we compared the differences in KIR repertoire of patients and healthy donors to investigate the reproducibility of previously reported significant differences between patients with hematological malignancies and healthy donors. The observed frequencies in our cohort volunteer HCT donors was comparable to those reported in neighboring Arab populations. The activating genes KIR2DS1, KIR2DS5 and KIR3DS1 and the inhibitory gene KIR2DL5 were significantly more frequent in patients compared to healthy donors, however, none of the previously reported differences were reproducible in our Kuwaiti cohort. This report is the first description of KIR gene carrier frequency and haplotype characterization in a fairly large cohort of the Kuwaiti population, which may have implications in KIR based HCT donor selection strategies.

Classification of major and minor blood group antigens in the Kuwaiti Arab population.

Ethnic differences in blood group frequencies might result in clinically important mismatches for transfusions. Arab people represent a large population for which no comprehensive database of red cell genotypes is available and Kuwaitis are no exception. For instance, the Rh blood group is the most elaborate blood group system that shows a high degree of polymorphism among different ethnic groups, there has been little classification of RH alleles in Arab people. Blood samples from 917 Kuwaiti Arab donors in the Kuwaiti Bone Marrow registry were tested with a single-nucleotide polymorphism DNA array. Blood group antigen prevalence were compared to known prevalence in European populations. Multiple subjects were found to be antigen negative for certain phenotypes that is considered rare by the American Rare Donor Program; (Fy(a-,b-) and Kell). In the minor blood group antigens, the FYA allele was predicted to be low in Kuwaitis, when compared to other published accounts. The frequencies of MNS blood antigens in the study population were not significantly different from those reported for European/Caucasian populations. The predicted frequency of the Diego blood group antigen was similar to that observed in a South Asian population. The weak D 1, 2, 3 phenotypes were not prevalent in the Kuwaiti Arab population; however, other RHD variants were detected. We provided information about blood group antigens in the Kuwaiti population that is important for guiding transfusion care. Several interesting findings demonstrated clinical importance, which could be useful in developing transfusion medicine policies and approaches.

HLA Haplotype Frequencies and Genetic Profiles of the Kuwaiti Population.

OBJECTIVE: The aim of this study was to assess the HLA haplotype frequencies and genetic profiles of the Kuwaiti population. MATERIALS AND METHODS: Whole venous blood was obtained from 595 healthy, unrelated Kuwaiti volunteers. The study population was genotyped for HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1 and HLA-DQB1) loci using sequence-specific oligonucleotide (SSO) probe-based hybridization and high-resolution HLA genotyping. Haplotype frequencies were estimated using an implementation of the expectation maximization algorithm that resolves both phase and allelic ambiguity. The Kuwaiti population was compared with other populations from the US National Marrow Donor Program (NMDP), by running a principal component analysis (PCA) on the relevant haplotype frequencies. RESULTS: The most common HLA class I alleles in Kuwait were HLA-A*02:01g, HLA-C*06:02g, and HLA-B*50:01g with frequencies of 16, 14, and 12%, respectively. The most common HLA class II alleles in Kuwait were HLA-DQB1*02:01g and HLA-DRB1*07:01 with frequencies of 29.7 and 16.5%, respectively. The most common Kuwaiti haplotype observed was HLA-A*02:01g∼HLA-C*06:02g∼HLA-B*50:01g∼HLA-DRB1*07:01∼HLA-DQB1*02:01g at a frequency of 2.3%. The PCA demonstrated close genetic proximity of the Kuwaiti population with Middle Eastern, Southeast Asian, and North African populations in the NMDP. CONCLUSION: Identifying the haplotype diversity in the Kuwaiti population will contribute to the selection of an HLA-match for HSCT, disease associations, pharmacogenomics, and knowledge of pop-ulation HLA diversity.

17th IHIW component "Immunogenetics of Ageing" - New NGS data.

The 'Immunogenetics of Aging' project is a component introduced in the 14th International HLA and Immunogenetics Workshop (IHIW) and developed further within subsequent workshops. The aim was to determine the relevance of immunogenetic markers, focusing on HLA, cytokine genes, and some innate immunity genes, for successful aging and an increased capacity to reach the extreme limits of life-span. Within the 17th IHIW we applied Next Generation Sequencing methods to refine further HLA associations at allele level in longevity, and to extend our knowledge to additional loci such as HLA-DQA1, HLA-DPB1 and HLA-DPA1. Analysis of relatively small number of healthy elderly and young controls from four populations showed that some HLA class I and class II alleles were significantly positively associated with healthy aging. Additionally we observed statistically significant differences in HLA allele distribution when the analysis was performed separately in elderly females and males compared to sex-matched young controls. Haplotypes, probably associated with better control of viral and malignant diseases were increased in the elderly sample. These preliminary NGS data could confirm our hypotheses that survival and longevity might be associated with selection of HLA alleles and haplotypes conferring disease resistance or susceptibility. Therefore HLA alleles and haplotypes could be informative immunogenetic markers for successful ageing.

Next-generation HLA typing of 382 International Histocompatibility Working Group reference B-lymphoblastoid cell lines: Report from the 17th International HLA and Immunogenetics Workshop.

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

Kuwait bone marrow transplantation activities.

Kuwait is located in the Arabian Gulf and has a population of 3.5million. The stem cell transplantation program started in 2000. Autologous peripheral blood stem cell transplantation started first, as it was easier technically to establish. In 2011, the allogeneic program started with focus on acute leukemia and hemoglobinopathies. The success of both programs required teamwork and support of health planners. The Kuwait National Bone Marrow Registry was established in 2012. The issue of donor availability and drug shortage remain the two main obstacles for expanding the bone marrow transplantation program.

Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era.

OBJECTIVE: PMBCL is a distinct type of nonhodgkins lymphoma with specific clinicopathological features. To clarify clinical features, treatment alternatives and outcomes, we evaluated 28 Arab patients treated with chemotherapy or radiotherapy between 2006 and 2011. PATIENTS AND METHODS: PMBCL lymphoma patients identified according to WHO classification and treated at KCCC between 2006 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A P < 0.05 was considered significant. RESULTS: The median age of the patients was 31 years and the male to female ratio was 2:1. Majority of the patients (75%) presented with stage I/II disease. Most had features of local extension like pleural effusion (18%) and SVCO (39%). Only 11% of the patients had bone marrow involvement at presentation. 96% of the patients required biopsy from the mediastinal mass either by image guided core biopsy (75%) or by surgical biopsy. Most patients were treated by RCHOP and involved field radiotherapy. Patients with positive PET scan after RCHOP chemotherapy received salvage chemotherapy and BEAM autologous marrow transplant. The five year OS for the entire group was 85% while the PFS was 73%. Patients who had PET scan for response evaluation had better OS [P = 0.013] and PFS [P = 0.039] when compared with those patients who received only radiotherapy based on CT scan evaluation. CONCLUSION: PMBCL is a specific lymphoma entity seen in the young with good survival. The role of PET scan for response evaluation and the type of consolidation therapy needs to be further clarified.

Mycosis fungoides in Arab children and adolescents: a report of 36 patients from Kuwait.

Mycosis fungoides (MF) is rare in children and adolescents. This study was aimed to determine the clinicoepidemiologic features of juvenile onset (≤18 yrs) MF in Kuwait. Thirty-six children and adolescents (≤18 yrs) with MF registered in a referral photobiology unit for cutaneous lymphomas between July 1991 and June 2009 were included in this study. Children and adolescents were observed to constitute 16.6% of the total number of patients with MF, with 97% of patients of Arab ethnicity. The age-adjusted incidence rate of MF in children and adolescents among the total population was 0.29/100,000 persons/year. Among 36 Arab children and adolescents, boys outnumbered girls by 1.25:1. Mean and median age at onset of disease was 9 years, and age at diagnosis was 13 years. Patch stage disease was the most common clinical variant (75%) with 56% with pure hypopigmented MF-variant. The majority of patients (75%) had stage IB (TNM and B staging) disease. The study highlights a high prevalence and incidence of juvenile MF in Kuwait with a predominantly hypopigmented presentation.

Clinicoepidemiological features of mycosis fungoides in Kuwait, 1991-2006.

BACKGROUND: Mycosis fungoides (MF) is an indolent, most common type of cutaneous T-cell lymphoma (CTCL) with an average estimated incidence of 0.5 cases per 100,000 persons per year in the western world. Although various clinical and epidemiological features are well delineated in the western population, the data is scarce from our region. OBJECTIVES: To study the clinicoepidemiological features of MF from Kuwait. SETTING: A referral photobiology unit for cutaneous lymphomas in a national dermatology department in collaboration with three other dermatology departments in Kuwait and Kuwait cancer center. PATIENTS AND METHODS: One hundred and ninety-three cases of MF registered between July 1991 and June 2006 were included for this study. RESULTS: Eighty-six percent of our MF cases were of Arab ethnicity. Males outnumbered the females by 2:1 ratio. Mean age at diagnosis was 35.20 ± 14.37 years, and 16% of the patients were diagnosed by the age 20 years. The annual incidence rate (IR) of MF in Kuwait was observed to be 0.43 cases per 100,000 persons with a significantly higher IR among Arabs as compared to non-Arab Asians (RR = 4.4; 95% CI = 2.9-6.6). A successive rise in the IR of MF was noticed with the advancing age. The annual IR among males was more or less comparable to that of females. Skin patches were the most prevalent skin lesions (67%) at diagnosis, and 22% of the patients had a pure hypopigmented variant. Patients with hypopigmented MF were observed to have younger mean age at diagnosis (27.60 ± 12.42 years) as compared to other MF cases (38.14 ± 14.37 years) (P = 0.000). Ninety-two percent of the patients had the early stage (IA, IB, and IIA) of disease. CONCLUSIONS: Our patients with MF were observed to have a relatively younger age at diagnosis, with a high proportion of patients diagnosed by the age 20 years. Arabs were observed to have a higher annual IR of MF as compared to non-Arab Asians. Hypopigmented MF is prevalent in our population. The study highlights the ethnic and/or regional variations in the clinicoepidemiological characteristics of MF.

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion.

BACKGROUND: Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. STUDY DESIGN AND METHODS: A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. RESULTS: Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. CONCLUSION: This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.

Role of serial quantitative gallium-67 tumor uptake in assessing response rates for chemotherapy in lymphoma patients.

PURPOSE: To evaluate in serial gallium-67 scans (GS) the role of semiquantitative tumor-to-background (Tm/Bg) and tumor-to-liver ratios in assessing response rates to chemotherapy, in Hodgkin's disease and non-Hodgkin's lymphoma. MATERIALS AND METHODS: Twenty-seven consecutive patients (15 Hodgkin's disease and 12 non-Hodgkin's lymphoma patients) with an average age of 30 (range, 5-60) years underwent GS at prechemotherapy, early chemotherapy (after first cycle), and postchemotherapy. Average tumor, background, and liver region of interest counts obtained and Tm/Bg, tumor-to-liver, and liver region to background ratios were derived for each patient on serial GS. All patients were assessed by visual and quantitative GS and followed up clinically for more than 7 years. RESULTS: At early visual GS, 70% (19 of 27) of the patients showed rapid response, 15% (four of 27) showed delayed response (negative at post-GS), and 15% showed no response. Mean early-GS Tm/Bg ratio of disease-free patients (1+/-0.04) was significantly different from relapsed (1.4+/-0.2) (P<0.025) and progressive disease (1.8+/-0.7) patients. A significant difference was noted (P<0.01) in serial paired comparisons of Tm/Bg ratios between pretherapy and early-therapy scans in relapsed patients, whereas progressive disease patients showed no significant change during the same time. At early-GS, 15 patients showed quantitative rapid response (Tm/Bg ratio 1.04), nine patients showed quantitative delayed response (Tm/Bg ratio >1.04 with significant serial change between pretherapy and early-therapy GS), and three patients showed quantitative no response (Tm/Bg ratio >1.04 with nonsignificant serial change between pretherapy and posttherapy GS). CONCLUSION: Quantitative GS is an effective tool in the detection of early response to chemotherapy. Quantitative response rates after the first cycle can more reliably identify patients who are most likely to be disease-free or relapse after first-line therapy or those that will show no response to therapy as compared with visual analysis alone.

Combined applications of fine needle aspiration cytology and flow cytometric immunphenotyping for diagnosis and classification of non Hodgkin lymphoma.

AIMS AND OBJECTIVES: In this present study we have evaluated the feasibility of sub-classification of non-Hodgkin's lymphoma (NHL) cases according to World Health Organization's (WHO) classification on fine needle aspiration cytology (FNAC) material along with flow cytometric immunotyping (FCI) as an adjunct. MATERIALS AND METHODS: In this five years study, only cases suggested or confirmed as NHL by FNAC were selected and FCI was performed with a complete panel of antibodies (CD3, CD2, CD 4, CD5, CD8, CD7, CD10, CD19, CD20, CD23, CD45, kappa and lambda) by dual color flow cytometry. Both cytologic findings and FCI data were interpreted together to diagnose and sub-classify NHL according to WHO classification. Wherever possible the diagnoses were compared with cytology. RESULTS: There were total 48 cases included in this study. The cases were classified on FNAC as predominant small cells (12), mixed small and large cells (5) and large cells (26). In five cases a suggestion of NHL was offered on FNAC material and these cases were labeled as NHL not otherwise specified (NHL-NOS). Flow cytometry could be performed in 45 cases (93.8%) and in rest of the three cases the material was inadequate because of scanty blood mixed aspirate. Light chain restriction was demonstrated in 30 cases out of 40 cases of B-NHL (75%). There were 15 cases each of kappa and lambda light chain restriction in these 30 cases. With the help of combined FCI and FNAC, it was possible to sub-classify 38 cases of NHL (79%) according to WHO classification. Combined FNAC and FCI data helped to diagnose 9 cases of small lymphocytic lymphoma (SLL), 2 cases of mantle cell lymphoma (MCL), 4 cases of follicular lymphoma (FL), 17 cases of diffuse large B lymphoma (DLBL) and 6 cases of lymphoblastic lymphoma. Histopathology diagnosis was available in 31 cases of NHL out of which there were 14 recurrent and 17 cases of primary NHL. Out of 15 DLBL cases diagnosed on FCI and FNAC, histology confirmed 14 cases and one of these cases was diagnosed as Burkitt's lymphoma on histology. Cases of FL (4), SLL (3) and MCL (2) were well correlated with histopathology. Out of the five cases suggestive of NHL on cytology, histopathology was available in four cases. Histology diagnosis was given as DLBL (1), SLL (1), anaplastic large cell lymphoma (1) and FL transformed into large cell NHL (1). Considering histopathology as gold standard, diagnostic specificity of combined FNAC and FCI was 100% (31/31) and sensitivity in sub-classification was 83.8% (26/31). CONCLUSION: FNAC combined with FCI may be helpful in accurately sub-classifying NHL according to WHO classification. Many of the subtypes of NHL such as FL and MCL which were previously recognized as a pure morphologic entity can be diagnosed by combined use of FNAC and FCI. Other ancillary investigations such as chromosomal changes, cell proliferation markers etc. may be helpful in this aspect.

Prevalence of viral markers among first-time Arab blood donors in Kuwait.

BACKGROUND: The aim of this study was to assess the effect of blood donation modes on the prevalence of viral markers among Arab first-time blood donors in Kuwait. STUDY DESIGN AND METHODS: Donor ethnic background was classified as Kuwaiti nationals and non-Kuwaiti Arabs. A total of 26,874 donors were screened in 2002 for the following viral markers: hepatitis C virus antibody (anti-HCV), hepatitis B surface antigen (HBsAg), anti-hepatitis B core antigen (HBc), human immunodeficiency virus-1 and -2 antibody (anti-HIV-1 and -2), HIV p24, and human T lymphotropic virus-I and -II antibody (anti-HTLVI/II). All samples positive for the presence of anti-HBc were tested for anti-HBs. Among these donors, 12,798 were first-time donors of which 74 percent were replacement and 26 percent were volunteers. RESULTS: The prevalence of HCV among replacement donors was significantly higher than the volunteer group. The difference between the two modes of blood donations, however, was not significant for HBsAg. The prevalence of anti-HCV among Kuwaiti national and non-Kuwaiti Arab first-time donors was 0.8 and 5.4 percent, respectively, whereas the prevalence of HBsAg was 1.1 and 3.5 percent, respectively, with the difference being significant at a p level of <0.0001. The difference observed for prevalence of anti-HBc among Kuwaiti national and non-Kuwaiti Arab donors (17 and 33.3%, respectively) was significant (p < 0.0001). Among first-time donors, 13.7 percent were positive for the presence of anti-HBs, indicating that 13.7 percent of the total Arab donor population might have had a previous infection and possible immunity to hepatitis B virus (HBV). CONCLUSION: A high prevalence of HBV and HCV was found among non-Kuwaiti Arab donors. The prevalence of anti-HCV was only significantly higher among replacement versus volunteer first-time donors. Therefore, there is a need to develop a strategic plan that incorporates the diverse background of the blood donors living in Kuwait.

Frequency of red blood cell alloantibody in Kuwaiti population.

OBJECTIVE: The aim of this study was to analyze the alloimmunization against red blood cells (RBC) among Kuwaiti population. MATERIALS AND METHODS: Retrospective analysis of RBC alloimmunization among 179,045 Kuwaiti patients, pregnant women, and allogeneic blood donors was conducted for the period of 1992-2001. The frequency of 24 alloantibody specificities from 1,278 alloimmunized Kuwaitis was estimated. RESULTS: The prevalence of positive antibody screen in Kuwait was 0.49%. The five most frequently identified alloantibodies were anti-D (27.3%), anti-E (18.5%), anti-K (15.6%), anti-Le(a) (8.7%), and anti-Le(b) (6.6%). Frequency of alloimmunization was greater among Kuwaiti female than male patients (3.2 F to 1 M). Anti-D (p<0.001), anti-E (p=0.05), anti-K (p=0.04) were also more frequently identified alloantibody among Kuwaiti females. CONCLUSION: The results show higher predominance of RBC alloimmunization in females than males. Anti-D, anti-E, and anti-K were the most common clinically significant alloantibodies identified in the Kuwaiti population and were also more frequent among Kuwaiti females.

The use of gallium-67 scintigraphy to monitor tumor response rates and predict long-term clinical outcome in patients with lymphoma.

The aim of this study was to determine whether gallium (Ga)-67 scintigraphy can monitor the treatment response rates and predict the long-term clinical outcome in patients with lymphoma. Gallium-67 scintigraphy was performed upon admission (baseline Ga) in 33 consecutive, newly diagnosed patients. Twenty-eight patients (Hodgkin's disease, n = 18; non-Hodgkin's lymphoma, n = 13) with Ga avid tumors were included in the study. All the patients were treated with induction chemotherapy. Gallium-67 scintigraphy was performed in all patients after the first cycle of chemotherapy (post-cycle 1 Ga) and repeated after the fourth cycle (post-cycle 4 Ga) or after completion of treatment (end-of-chemotherapy Ga). Nineteen patients had a fast response (68%, negative in post-cycle 1 and end-of-chemotherapy Ga), 4 intermediate response (14%, partial positive post-cycle 1 Ga that progressed to negative post-cycle 4 Ga), 3 slow response (11%, partial positive in both post-cycle 1 and post-cycle 4 Ga) and 2 no response (7%, positive in both post-cycle 1 and end-of-chemotherapy Ga). In patients who had either fast or intermediate response, 22 (96%) were free of disease at a median follow-up period of 30 months (range, 11-45 months). All 5 patients (100%) who had slow or no response had progressive disease or residual disease. In conclusion, the findings indicate that Ga could effectively be used to monitor the treatment response rates and predict the long-term clinical outcome in patients with lymphoma and should be used in treatment modifications aimed at reducing toxicity of effective therapy in patients with fast response and replacing treatments early in patients with slow or no response.

Hodgkin's disease: Kuwait experience.

OBJECTIVE: To describe histologic subtypes, clinical presentation and treatment outcome of Hodgkin's lymphoma in Kuwait. SUBJECTS AND METHOD: Patients older than 15 years, diagnosed with Hodgkin's lymphoma between 1980 and 1998, were included in this retrospective analysis. Data were collected using a standardized form that included demographics, histologic subtypes, clinical presentation, stage, extranodal involvement, treatment modality and follow-up. Histology reports were obtained from hospital records. RESULTS: There were 83 (59%) males and 57 (41%) females. Dominant histologic subtypes were nodular sclerosis 65 (46.4%) and mixed cellularity 42 (30%). Constitutional symptoms were reported by 54 (38.6%) of the cases. Two thirds (64%) of the cases were advanced. Primary extranodular involvement included liver (8%), gastrointestinal tract (7%), lung and bone marrow (4% each). Disease-free survival according to treatment groups were: radiotherapy alone 100%, chemotherapy alone 88%, and combined modality 65%. The 5-year Kaplan-Meier estimates of overall disease-free survival was 84%. CONCLUSION: In the cohort of 137 patients with Hodgkin's disease the treatment with combined radiotherapy and chemotherapy had a remarkable outcome. However, evaluation of long-term treatment complications is needed.

Monoclonal gammopathy among patients with chronic hepatitis C infection.

OBJECTIVE: To determine the prevalence of monoclonal gammopathies in Kuwait and its association with chronic hepatitis C virus (HCV) infection. METHODOLOGY: Serum protein electrophoresis and measurement of immunoglobulin levels were carried out prospectively in 100 consecutive patients with chronic HCV infection. RESULTS: Among the 100 patients tested (82 males, 18 females; median age 45 years), 59 had polyclonal band in serum protein electrophoresis while the other 41 had a normal pattern. None of the patients had monoclonal gammopathy. The mean serum immunoglobulin levels were: IgG 18.4 g/l (range 4-39), IgA 2.9 g/l (range 0.09-8) and IgM 1.6 g/l (range 0.14-6.08). CONCLUSION: There was no evidence of monoclonal gammopathies in patients with chronic HCV infection in Kuwait.

RBC alloimmunization and autoimmunization among transfusion-dependent Arab thalassemia patients.

BACKGROUND: Thalassemia major is a common hemoglobinopathy in the Arabian Gulf region. However, limited data are available on the frequency of RBC alloimmunization and autoimmunization in transfusion-dependent Arab thalassemia patients. STUDY DESIGN AND METHODS: A total of 190 thalassemia major patients were classified as Kuwaiti Arab and non-Kuwaiti Arab. Pretransfusion investigation records were reviewed for the presence of RBC alloantibody and autoantibody, and the age at which RBC alloantibody was developed. RESULTS: Fifty-seven (30%) patients developed RBC alloantibodies. The most common clinically significant alloantibodies were directed against antigens in the Kell and Rh systems. Anti-K developed in 41 (72%) patients followed by anti-E in 26 (45.6%). RBC autoantibodies developed in 21 (11%) patients with and without underlying RBC alloantibodies. Sixty-six (49.6%) RBC alloantibodies developed between the ages of 2 and 10 years. CONCLUSION: Several factors might have contributed to the high alloimmunization and autoimmunization rate observed in this study, including the heterogeneity of the population living in Kuwait, lack of better-matched donors for those patients, and the use of poststorage leukodepleted blood. It is recommended that thalassemia patients receive blood matched for Rh and Kell antigens and prestorage leukodepleted RBCs.