Initial flow cytometric evaluation of the Clearllab lymphoid screen.

INTRODUCTION: Flow cytometric immunophenotyping (FCI) is an integral part in the diagnosis and classification of hematologic malignancies. FCI results also influence therapeutic decisions and disease prognosis. ClearLLab LS is a 12-antibody 10-color cocktail provided in dry format designed as a screen for patients suspected of having hematolymphoid disease. METHODS: A blinded comparison between ClearLLab LS, (CD8-FITC, Kappa-FITC,CD4-PE, Lambda-PE, CD19-ECD, CD56-PE-Cy5.5, CD10-PE-Cy7, CD34-APC, CD5-APC-A700, CD20-APC-A750, CD3-PB, and CD45-KrO), ClearLLab Reagents (five-color, 17-antibodies) and individual Laboratory Developed Tests (LDTs), was conducted at four laboratories. Evaluation of ClearLLab LS was performed on 210 specimens, compared to the five-color ClearLLab Reagents (IVD and CE-IVD), and a subset (n = 167) to LDTs. RESULTS: ClearLLab LS showed good agreement to ClearLLab Reagents in detecting the absence (104/104) or presence (106/106) of abnormal populations. Of specimens with abnormal populations the ClearLLab LS agreed with the ClearLLab Reagent for neoplasm maturity assessment (70/70 mature and 36/36 immature). Out of 167 specimens with LDTs results, 86 contained abnormal population(s), ClearLLab LS detected 82 (95.3%) of cases. Of the 4 cases not detected by ClearLLab LS, 3 were plasma cell neoplasms and 1 was a mature T cell malignancy. Eighty-one samples with no hematological malignancy as analyzed by LDT were also negative by ClearLLab LS (100% agreement). ClearLLab LS agreed with LDTs assessment of neoplasms' maturity (55/55 mature and 27/27 immature). CONCLUSION: ClearLLab LS screening tube showed excellent agreement between ClearLLab Reagents and with LDT's. The presence of CD34 and CD10 in the tube allowed the detection of blast populations in several acute leukemias and myeloid neoplasms that were tested. © 2017 International Clinical Cytometry Society.

Enrolment and retention of people who inject drugs in the Needle & Syringe Exchange Programme in Malaysia.

Setting: Needle and Syringe Exchange Programme (NSEP) implemented by non-governmental organisations in Malaysia. Objectives: To determine enrolment, characteristics and retention in the NSEP of people who inject drugs (PWID) between 2013 and 2015. Design: Retrospective cohort study. Results: There were 20 946 PWID, with a mean age of 38 years. The majority were male (98%) and of Malay ethnicity (92%). Follow-up data were available for 20 761 PWID. Annual retention of newly enrolled PWID for each year was respectively 85%, 87% and 78% for 2013, 2014 and 2015, although annual enrolment over these years declined from 10 724 to 6288 to 3749. Total person-years (py) of follow-up were 27 806, with loss to follow-up of 40 per 100 py. Cumulative probability of retention in NSEP was 66% at 12 months, 45% at 24 months and 26% at 36 months. Significantly higher loss to follow-up rates were observed in those aged 15-24 years or ⩾50 years, females, transgender people and non-Malay ethnic groups. Conclusion: Annual retention of new PWID on NSEP was impressive, although enrolment declined over the 3 years of the study and cumulative loss to follow-up was high. A better understanding of these programmatic outcomes is required.

Contexte: Programme d'échange d'aiguilles et de seringues (NSEP) mis en œuvre par des organisations non-gouvernementales en Malaysie.Objectif: Déterminer l'enrôlement, les caractéristiques et la rétention dans le NSEP des personnes qui s'injectent des drogues (PWID) entre 2013 et 2015.Schéma: Etude rétrospective de cohorte.Résultats: Il y a eu 20 946 PWID, dont l'âge moyen a été de 38 ans. La majorité a été de sexe masculin (98%) et d'ethnie malaise (92%). Les données de suivi ont été disponibles pour 20 761 PWID. Le taux de rétention annuel des PWID nouvellement enrôlés a été de 85%, 87% et 78% pour 2013, 2014 et 2015, respectivement, bien que l'enrôlement annuel ait décliné de 10 724 à 6288, puis à 3749. Le suivi total en personnes-années (py) a été de 27 806, avec des pertes de vue de 40 pour 100 py. La probabilité cumulative de rétention dans le NSEP a été de 66% à 12 mois, de 45% à 24 mois et de 26% à 36 mois. Des taux de perdus de vue significativement plus élevés sont survenus chez les patients âgés de 15 à 24 ans ou ⩾50 ans, de sexe féminin, transgenre et d'un groupe ethnique autre que malais.Conclusion: La rétention annuelle des nouveaux PWID dans la NSEP a été impressionnante, bien que l'enrôlement ait décliné sur les 3 ans de l'étude et que les pertes de vue cumulées aient été élevées. Une meilleure compréhension de ces résultats du programme est requise.

Marco de referencia: El programa nacional de intercambio de agujas y jeringuillas introducido (NSEP) por organizaciones no gubernamentales en Malasia.Objetivos: Describir la inscripción, la permanencia y las características de las personas consumidoras de drogas inyectables (PWID) que participaron en el programa NSEP entre el 2013 y el 2015.Método: Fue este une estudio retrospectivo de cohortes.Resultados: Se inscribieron en el programa 20 946 PWID, cuya edad promedio fue 38 años. La mayoría era de sexo masculino (98%) y de etnia malaya (92%). Se practicó el seguimiento de 20 761 personas. La tasa anual de permanencia en el programa de los recién inscritos fue 85% en el 2013, 87% en el 2014 y 78% en el 2015, pero la tasa inscripción anual disminuyó de 10 724 a 6288 y 3749 personas, respectivamente. Se logró un seguimiento total de 27 806 años-persona (py), con una pérdida durante el seguimiento de 40 por 100 py. La probabilidad acumulada de permanencia en el programa fue 66% a los 12 meses, 45% a los 24 meses y 26% a los 36 meses. Las pérdidas durante el seguimiento fueron significativamente mayores en el grupo de 15 a 24 años de edad o a partir de los 50 años, en las mujeres, las personas transgénero y los grupos étnicos diferentes al malayo.Conclusión: La tasa anual de retención de las PWID recién inscritas en el programa NSEP fue sorprendente, pese a que las inscripciones disminuyeron durante los 3 años y las pérdidas acumuladas durante el seguimiento fueron altas. Es necesario ampliar la comprensión de estos resultados programáticos.

Flow cytometry-Recognizing unusual populations in leukemia and lymphoma diagnosis.

Flow cytometry is an invaluable technology in the examination of blood, bone marrow, tissue and body fluids for the presence or absence of hematological disease. It is used in both diagnostic and follow-up testing, with an increasingly important role in the detection of very small residual disease populations (Minimal Residual Disease, MRD) However, flow cytometry immunophenotyping of leukemia and lymphoma is highly dependent on interpretation of results and with the increased complexity of 8-10 color instruments routinely used in clinical laboratories, knowledge of disease-defining populations is increasingly important as is recognizing normal and reactive patterns. This manuscript presents case studies with flow cytometric patterns encountered in routine screening of samples sent for leukemia and lymphoma immunophenotyping, focusing mainly on B-cell disorders which may be missed or incorrectly interpreted by the laboratory (including a hematopathologist) performing the test. Case studies are used to illustrate our laboratory's standardized approach to the interpretation of flow cytometric data. In addition to a standardized approach, these cases emphasize the importance of interpretative skills of technologist and hematopathologists in recognizing abnormal patterns in detecting hematological malignancies.

Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia.

BACKGROUND: We used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment. METHODS: The study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a case-based scenario using 0%-100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. RESULTS: Of 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki. CONCLUSIONS: Given the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki.

Reproductive decision making after the diagnosis of multiple sclerosis (MS).

OBJECTIVE: This study aimed to determine reproductive practices and attitudes of North Americans diagnosed with multiple sclerosis (MS) and the reasons for their reproductive decision making. METHODS: A self-administered questionnaire on reproductive practices was mailed to 13,312 registrants of the North American Research Committee on Multiple Sclerosis (NARCOMS) database who met inclusion criteria for the study. Completed questionnaires were then returned to the authors in an anonymous format for analysis. RESULTS: Among 5949 participants, the majority of respondents (79.1%) did not become pregnant following diagnosis of MS. Of these, 34.5% cited MS-related reasons for this decision. The most common MS-related reasons were symptoms interfering with parenting (71.2%), followed by concerns of burdening partner (50.7%) and of children inheriting MS (34.7%). The most common reason unrelated to MS for not having children was that they already have a "completed family" (55.6%). Of the 20.9% of participants who decided to become pregnant (or father a pregnancy) following a diagnosis of MS, 49.5% had two or more pregnancies. CONCLUSION: This study indicates that an MS diagnosis does not completely deter the consideration of childbearing in MS patients of both genders.

A proposed methodology to estimate the cumulative life-time UVB exposure using geographic information systems: An application to multiple sclerosis.

BACKGROUND: The cause of multiple sclerosis (MS) is unknown; multiple risk factors have been implicated, including environmental exposures, such as sunlight. Many studies have relied on latitude alone as a crude proxy for sunlight exposure. We aimed to develop a protocol allowing a more detailed estimate of cumulative ambient ultra-violet B (UVB) exposure at critical time-periods over a patient's life-course. METHODS: 4010 definite MS patients with a 'movement history' from birth to the study end (2005) were selected from the University of British Columbia, Canada's MS Genetic database. Patient's place of resident from birth were tracked, each place being geocoded (latitude and longitude) and assigned a UVB value using the NASA Total Ozone Mapping Spectrometer (TOMS) dataset. Combined, these data allowed an estimated UVB value for each patient based on year and location. RESULTS: Using this protocol, we provide a potentially more detailed cumulative UVB exposure for critical periods in a patients' life history based on their individual spatial migration through time. CONCLUSIONS: This protocol is intended to provide a framework for researchers to more accurately estimate UVB exposures for individuals over the course of their life history and may be useful for understanding etiology of MS and other chronic disease.

Enhanced flagging and improved clinical sensitivity on the new DxH 300(TM) Coulter(®) cellular analysis system.

INTRODUCTION: The Beckman Coulter DxH 300™ is a hematology analyzer that performs a CBC and 3-part WBC differential and incorporates new electronic, algorithm and mechanical design. METHODS: This instrument was compared with the predicate analyzer (Coulter(®) A(c) ·Tdiff2) and the larger format Coulter LH780 analyzer. Of interest were flagging rates, clinical sensitivity, and accuracy of the WBC in the presence of interfering particles. The total sample set (n = 404) consisted of morphologically normal and hematologically abnormal patients. RESULTS: Correlation of the DxH 300 with A(c) ·Tdiff2™ showed good agreement with all directly measured parameters. When compared with the LH780, WBC and platelets (PLT) counts showed good agreement with small biases. Importantly in the low range (PLT <50 × 10(9) /L), there was a small positive bias of only 2 × 10(9) /L PLT. Interfering particles did not affect the DxH 300 WBC count (P > 0.05) with strong correlations to the LH780 (r(2) values >0.95). Importantly, overall and specific flagging rates as well as false-negative and false-positive rates were significantly reduced on the DxH 300 compared with the A(c) ·Tdiff2 (27% and 41% reduction, respectively, P < 0.001). CONCLUSIONS: The DxH 300 offers significant improvement over the predicate Coulter analyzer in flagging rates and improved correlation with larger format analyzers for WBC and PLT counts. Reduced false negatives and false positives significantly improved sensitivity and specificity compared to the predicate analyzer. The 28% improvement in flagging efficiency together with numerous software and data handling enhancements should translate into reduced need to perform follow-up analysis on a significant number of samples.

Initial performance evaluation of the UniCel® DxH 800 Coulter® cellular analysis system.

The Beckman Coulter UniCel® DxH 800 is a hematology analyzer incorporating new electronic and mechanical design with advanced algorithm technology to perform CBC, white blood cell (WBC) differential, nucleated red blood cell (NRBC), and reticulocyte analysis. Evaluation of this instrument was performed in our 800-bed tertiary care hospital and specifically centered upon the correlation of WBC, NRBC, and platelet (PLT) enumeration when compared to a predicate analyzer, the Coulter® LH 780, and flow cytometry (FCM) reference methods. Of particular interest were those samples with morphologically confirmed interference and extreme leukocytosis (evaluated with respect to red blood cell parameter correction). The sample set (n=272) consisted of morphologically normal and hematologically abnormal patients. Correlation of the WBC, PLT, and NRBC showed r(2) values of 0.994, 0.985, and 0.910 for the DxH 800 vs. FCM, respectively. The presence of interfering particles did not affect the accuracy of the DxH 800 with respect to WBC counts. The DxH 800 showed accurate PLT and NRBC counts in the clinically significant low range when compared to FCM. Compared to the LH 780, flagging rates were significantly reduced (NRBC flag), or equivalent (WBC, PLT flag) on the DxH 800. The DxH 800 demonstrated higher sensitivity and specificity for PLTs and NRBCs and achieved a lower NRBC false negative rate compared to the LH 780. The UniCel® DxH 800 represents a significant improvement to previous impedance analyzers in accurately detecting the presence of NRBCs at counts >1/100 WBC. Furthermore, it provides accurate PLT and WBC counts in the presence of interference and improved NRBC flagging efficiency when compared to the LH 780. Correction of red blood cell parameters is appropriate and accurate in cases of extreme leukocytosis.

Access to thalidomide for the treatment of multiple myeloma in Canada: physician behaviours and ethical implications.

BACKGROUND: Multiple myeloma is an incurable malignancy. Since the late 1990s, its management has changed with the introduction of novel agents. Thalidomide, which is often called a "novel" therapy, has significantly prolonged survival in multiple myeloma and is considered worldwide to be part of standard of care in this disease. However, thalidomide is not approved in Canada, leading to problems with drug access for patients. METHODS: Our study surveyed Canadian hematologists on their thalidomide prescribing practices and difficulties with drug access. We address some of the ethical issues facing patients and their doctors who are unable to obtain or afford the drug, and who therefore resort to alternative means such as illegal importation. RESULTS: Of the 411 Canadian hematologists contacted, 122 completed the survey, 97 reported that they did not treat myeloma, and 192 did not respond. Assuming that all non-responders treat myeloma, our estimated overall response rate from physicians who treat this disease was 39%. Survey participants indicated that, in Canada, access to thalidomide is a major issue for physicians and myeloma patients alike, and that 81% of respondents are dissatisfied or very dissatisfied with the drug access process. Many physicians felt that the special access process for thalidomide is unduly onerous, influences treatment decisions, and invades patient privacy. We found that 20% of physicians were unaware of the legal implications of obtaining thalidomide from other countries and that at least 23% overtly or covertly support patients in obtaining the drug from a non-Health-Canada-approved source. CONCLUSIONS: The current lack of access to thalidomide in Canada is a concerning problem for patients and health care providers dealing with myeloma. Regulatory changes at the federal level (Health Canada) need to be re-examined to promptly resolve this issue.

Disease onset in familial and sporadic primary progressive multiple sclerosis.

The pathophysiology of primary progressive (PP) multiple sclerosis (MS) involves diffuse axonal degeneration which is believed to start early in the disease process, even before the onset of clinical symptoms. Symptomatic onset then occurs when this process reaches a threshold after which the axonal loss can no longer be compensated. A preliminary study showed that patients with familial PPMS had an earlier clinical onset than patients with sporadic disease, suggesting a hereditary component to the disease process of PPMS. In this study, we combined data from two large, population-based, longitudinal MS databases to investigate disease onset in familial and sporadic PPMS. We examined 411 patients with PPMS. There were no differences in gender distribution or onset symptoms between familial and sporadic PPMS. Patients with familial PPMS were significantly younger at disease onset (n = 84, median age: 37.6 years) than patients with sporadic disease (n = 327, median age: 42.7, p = 0.007). This difference was due to a greater proportion of familial cases with a disease onset before the age of 30 and a smaller proportion with disease onset between 40 and 50 years of age (p = 0.002). Gender had no significant effect on the age at disease onset. Further analyses showed that these findings were unlikely to be due to ascertainment bias towards an earlier diagnosis in familial cases. Our findings suggest a hereditary component to the disease process of PPMS. It would be worthwhile to identify patients with familial PPMS for future research on disease modifying genes in MS.

Sex ratio of multiple sclerosis and clinical phenotype.

BACKGROUND AND PURPOSE: In a longitudinal population-based dataset of patients with multiple sclerosis (MS), we have previously observed a substantial increase in the female to male sex ratio in Canada over the last 50 years. Here, we aimed to determine whether this change in sex ratio is related to the clinical course of MS. METHODS: We calculated sex ratios by birth year in 11 868 patients with relapsing-remitting (RR) MS and 2825 patients with primary progressive (PP) MS identified as part of the Canadian Collaborative Project on the Genetic Susceptibility to MS. RESULTS: Year of birth was a significant predictor for sex ratio in RR MS (P < 0.0001, chi(2) = 21.2; Spearman's rank correlation r = 0.67), but not for PP MS (P = 0.44, chi(2) = 0.6; Spearman's rank correlation r = 0.11). CONCLUSIONS: An increase in the number of female RR MS patients over time accounts for the increasing sex ratio of MS. This has implications for pathogenesis, for assessment of clinical trial results and for disease prevention. The factors underlying the selective increase in MS in females need to be uncovered.

Effect of immigration on multiple sclerosis sex ratio in Canada: the Canadian Collaborative Study.

BACKGROUND: The ratio of female to male (F:M) multiple sclerosis (MS) cases varies geographically, generally being greater in areas of high prevalence. In many regions, including Canada, rising MS incidence in women has been implied by the marked increase in F:M ratio. METHODS: We examined the F:M ratio over time in MS patients in the Canadian Collaborative Study born outside Canada, with onset postmigration (n = 2531). We compared the trends to native-born Canadians, by region of origin and age at migration. RESULTS: Regression analysis showed that year of birth (YOB) was a significant predictor of sex ratio in immigrants (chi(2) = 21.4, p<0.001 correlation r = 0.61). The rate of change in sex ratio was increasing in all migrant subgroups (by a factor of 1.16 per 10-year period, p<0.001), with the steepest increase observed in those from Southern Europe (1.27/10 years, p<0.001). The overall immigrant F:M ratio was 2.17, but varied by country of origin. It was significantly lower in migrants from Southern Europe compared with Northern Europe or USA (1.89 vs 2.14 and 2.86, p = 0.023 and p = 0.0003, respectively). Increasing age at immigration was associated with decreasing sex ratio (p = 0.041). The sex ratio of individuals migrating <21 was significantly higher than those migrating > or =21 (2.79 vs 1.96, p = 0.004). CONCLUSIONS: MS sex ratio in immigrants to Canada is increasing but variable by region of origin and influenced by age at migration. The findings highlight the importance of environmental effect(s) in MS risk, which are likely gender-specific.

Parent-of-origin effect in multiple sclerosis: observations from interracial matings.

BACKGROUND: Multiple sclerosis (MS) is a complex neurologic disease with a striking geographical distribution. In Canada, prevalence is high in Caucasians of Northern European ancestry and uncommon in North American Aboriginals, many of whom now have Caucasian admixture. METHODS: The population-based Canadian Collaborative Project on the Genetic Susceptibility to MS provided the characteristics of 58 individuals with 1 Caucasian and 1 North American Aboriginal parent from a database of 30,000 MS index cases. RESULTS: We found that MS index cases with a Caucasian mother and a North American Aboriginal father had a higher sib recurrence risk and greater F:M sex ratio (p = 0.043) than patients with a North American Aboriginal mother and Caucasian father. CONCLUSIONS: Maternal parent-of-origin effects in multiple sclerosis disease etiology previously seen in studies of half-siblings and avuncular pairs are also seen in Caucasian-North American Aboriginal admixture matings and warrant further investigation. A differential influence of maternal risk transmission on the sex ratio of affected offspring is implied. The method of analysis used may have broader implications for detection of parent-of-origin effects in admixture cohorts.

Recombinant activated factor VII in the treatment of non-haemophilia patients: physician under-reporting of thromboembolic adverse events.

The objective of this study was to determine if clinically important thromboembolic adverse events (TAEs) because of recombinant activated factor VII (rFVIIa) administration are being under-reported. rFVIIa is a potent haemostatic agent with a short half-life of 2.6 h that is increasingly used in 'off-label' situations. Retrospective review of 94 patients who received rFVIIa during 1 January 2003 to 30 June 2007 was carried out at a tertiary care centre. Sixty-nine patients, 32 females and 37 males, mean age 55 years (18-84 years), satisfied study criteria of off-label usage. This was a high-risk population with 33 (48%) deaths. A mean dose of 8.2 mg (2.4-19.2 mg) was administered in two average divided doses. Thirty-six potential TAEs were identified in 29 patients, and of these, 12 patients had TAEs deemed to be rFVIIa related and were identified on average 8.8 days after exposure to rFVIIa. Forty-eight (70%) physician questionnaires were completed; however, no TAEs were reported in these questionnaires or on chart review. Potential clinically significant TAEs are being under-reported by treating physicians. Until further evidence, we suggest the urgent need to develop consensus recommendations for utilization and required follow up to monitor the safety of rFVIIa and that at a minimum, all use of rFVIIa should be regulated through a gate-keeping mechanism that ensures adherence to these policies. Furthermore, prospective registries and trials are necessary to evaluate the efficacy and safety of rFVIIa in off-label settings.

Age of puberty and the risk of multiple sclerosis: a population based study.

BACKGROUND AND PURPOSE: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Given a potential role for sex hormones in MS, we have investigated whether or not the age of puberty influences the risk of developing MS in a population-based cohort. METHODS: We identified 5493 MS index cases and 1759 spousal controls with age of puberty information from the Canadian Collaborative Project on Genetic Susceptibility to MS. Age of puberty was compared between index cases and controls, and any effect of age of puberty on the age of onset of MS was also investigated. RESULTS: There were no significant differences between male index cases and controls with respect to age of puberty, P = 0.70. However, a significant difference was observed between female index cases and female controls, with average age of puberty being 12.4 and 12.6 years respectively, P = 0.00017, providing a relative risk decrease of 0.9 per year increase of age of puberty. There was no effect of the age of puberty on the age of MS onset in either sex. CONCLUSIONS: Earlier age at menarche increases the risk of MS in women. Whether this association is a surrogate for a disease causative factor or directly involved in MS disease aetiology needs to be uncovered.

A timing-of-birth effect on multiple sclerosis clinical phenotype.

BACKGROUND: A month-of-birth (MOB) effect has been shown in multiple sclerosis (MS). METHODS: Our chi(2) analyses looked at whether this MOB effect differed by MS phenotype ("bout onset," "primary progressive"). RESULTS: The MOB effect was derived from "bout onset" MS patients (May/November ratio = 1.43; chi(2) = 17.32, df = 1, p = 0.000032). CONCLUSIONS: An unspecified environmental effect in early development can influence both multiple sclerosis susceptibility and phenotype.

Parental transmission of MS in a population-based Canadian cohort.

OBJECTIVE: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. The precise nature of these factors and mode of inheritance remains unknown. A female predominance is universally found. Recently, offspring of affected fathers were reported to be more likely to have MS than those of affected mothers. This was attributed to the Carter effect, which is seen in polygenic disorders. The Carter effect predicts that affected parents of the sex lesser affected by a disease/trait are more genetically loaded for risk alleles and thus transmit these more often to their offspring. This hypothesis was tested in a population-based Canadian MS cohort. METHODS: Using the longitudinal Canadian database, we identified 3,088 nuclear families with one affected parent and a total of 8,401 offspring, of which 798 had MS. Transmission to daughters and sons from affected mothers and fathers was compared. RESULTS: There was equal transmission of MS from affected fathers vs affected mothers (9.41% vs 9.76%). Stratifying by gender of affected parent there were no differences in the female:male sex ratio of affected (2.46% vs 2.41%, p = 0.88) or unaffected offspring (0.91% vs 0.95%, p = 0.46). CONCLUSIONS: We observed equal disease transmission to offspring from affected mothers and affected fathers, no difference in the female:male sex ratio of affected offspring, and previously no difference in sibling recurrence risk by gender of parent affected. These findings show no evidence for the Carter effect and do not support the hypothesis of polygenic inheritance of multiple sclerosis susceptibility by parent.