The Manchester Scoring System for predicting BRCA1/2 mutations underperforms in Arabic Omani breast cancer patients.

Risk assessment models that are applied to assess the lifetime risk of cancer and pathogenic variant risk are more commonly used in Western populations. Using these models, without validation, for non-Western populations has been questioned. This study aimed to evaluate the use and consistency of the Manchester Scoring System as a risk assessment model for the Omani population. A retrospective, file-based analysis was performed on breast cancer patients seen in a genomics department over a two-year period. Personal cancer history and family history were used to analyze the Manchester scores of 409 breast and/or cancer patients. The results show that, overall, the Manchester scores were low. If this risk assessment model had been used to determine eligibility for a priori service and genetic testing decisions, 12 BRCA pathogenic cases would have been missed. At this time, the Manchester Scoring System does not seem to be the best risk assessment model for use in the Omani population, unless the eligibility threshold of ≥6 is used, which could provide a better sensitivity for the Omani population. We propose using concepts of the Manchester Scoring model to create a scoring system that is more suitable for the Omani and Arabic population.

Comparison of toxicity following single versus tandem autologous transplant regimens for pediatric medulloblastoma.

BACKGROUND: Medulloblastoma outcomes have improved with craniospinal irradiation and chemotherapy, but such therapy has resulted in poor neurocognitive outcomes for young patients. Chemotherapy-only regimens with autologous transplant have been implemented with the intention of avoiding radiation. It is not yet known whether single or tandem transplantation is superior with respect to efficacy and/or safety. METHODS: We performed a retrospective review of children with medulloblastoma treated at Dana-Farber Cancer Institute from 1996 to 2016 who received either single or tandem autologous transplantation after completion of induction chemotherapy. We compared safety and outcome data between the two groups. RESULTS: Among 23 patients, 12 received tandem transplants. Median follow-up was 6.4 years (IQR = 0.8-10.5). There was no statistically significant difference in 5-year EFS or OS between the single (70.7 ± 14%, 80.2 ± 13%) and tandem transplant groups (57.1 ± 15%, 79.6 ± 13%). Seven tandem transplant patients received subsequent radiation while only four required radiation in the single transplant group (p = .41). In the single transplant regimen, patients experienced longer antibiotic duration (p = .03) and LOS (p = .01) and a trend toward increased number of transfusions (p = .06). Four cases of veno-occlusive disease were reported in the single transplant group (p = .04). CONCLUSIONS: Outcomes were similar between regimens, but the single transplant regimen had more hepatic complications. These data suggest that tandem transplant regimens may have reduced toxicity compared to the single transplant regimen with similar outcome measures.

Feasibility and acceptability of the "Day 100 Talk": An interdisciplinary communication intervention during the first six months of childhood cancer treatment.

BACKGROUND: Communication gaps arise early in the childhood cancer trajectory and may persist. The authors conducted a pilot study of the feasibility and acceptability of a communication intervention, the Day 100 Talk (D100). D100 involves an interprofessional family conference during initial months of treatment between oncologists, psychosocial clinicians, and parents, facilitated by a 3-part conversation tool. METHODS: The authors enrolled English-speaking parents of children with nonrelapsed, nonprogressive cancer who were receiving continuity care from enrolled pediatric oncologists and psychosocial clinicians at a single site. The a priori feasibility threshold was 60% parent completion of the D100 intervention. Surveys from parents and professionals and debrief interviews with professionals assessed D100 acceptability. RESULTS: Thirty-seven parents (77%) and 38 oncology professionals (67%) enrolled. Twenty of 33 evaluable parents (61%) participated in a D100 family conference. Most commonly, parents did not complete the D100 intervention because of scheduling difficulties related to clinical team constraints. All 17 parents who completed a post-D100 survey agreed or strongly agreed that D100 participation was helpful. In debrief interviews, professionals identified D100 benefits, namely, stepping back to the big picture and getting on the same page, and barriers related to logistical challenges and professionals' anticipatory dread. CONCLUSIONS: The D100 intervention pilot demonstrates high acceptability among parents of children with cancer. Despite meeting the prespecified feasibility threshold, findings highlight important barriers to D100 dissemination, namely, perceived burdens on professionals. Potential strategies to reduce burden may include using virtual visit platforms, incorporating D100 elements across multiple visits, or prioritizing intervention delivery to parents with the greatest need for enhanced communication.

The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency.

Diagnosis of pyruvate kinase deficiency (PKD), the most common cause of hereditary non-spherocytic haemolytic anaemia, remains challenging in routine practice and no biomarkers for clinical severity have been characterised. This prospective study enrolled 41 patients with molecularly confirmed PKD from nine North American centres to evaluate the diagnostic sensitivity of pyruvate kinase (PK) enzyme activity and PK:hexokinase (HK) enzyme activity ratio, and evaluate the erythrocyte PK (PK-R) protein level and erythrocyte metabolites as biomarkers for clinical severity. In this population not transfused for ≥90 days before sampling, the diagnostic sensitivity of the PK enzyme assay was 90% [95% confidence interval (CI) 77-97%], whereas the PK:HK ratio sensitivity was 98% (95% CI 87-100%). There was no correlation between PK enzyme activity and clinical severity. Transfusion requirements correlated with normalised erythrocyte ATP levels (r = 0·527, P = 0·0016) and PK-R protein levels (r = -0·527, P = 0·0028). PK-R protein levels were significantly higher in the never transfused [median (range) 40·1 (9·8-73·9)%] versus ever transfused [median (range) 7·7 (0·4-15·1)%] patients (P = 0·0014). The PK:HK ratio had excellent sensitivity for PK diagnosis, superior to PKLR exon sequencing. Given that the number of PKLR variants and genotype combinations limits prognostication based on molecular findings, PK-R protein level may be a useful prognostic biomarker of disease severity and merits further study.

Thinking ahead: Parents' worries about late effects of childhood cancer treatment.

BACKGROUND: Many childhood cancersurvivors experience at least one late effect of treatment, and both late effects and persistent cancer-related worry can negatively impact quality of life in survivorship. Little is known about the prevalence or impact of parental worry about late effects early in treatment. This study evaluated parental perceived likelihood, impact, and worry about late effects of childhood cancer. PROCEDURE: We surveyed 96 parents of pediatric cancer patients at Dana-Farber/Boston Children's Cancer and Blood Disorders Center within a year of diagnosis. Parents were asked about their experiences with late effects communication, general worry about late effects, and specific late effect worries. RESULTS: Most (96%) parents valued information about late effects, and 93% considered late effects in their treatment decision-making. Yet, 24% could not recall receiving any information about late effects, and only 51% felt well prepared for potential late effects. Though only 20% of parents considered their child at high risk of experiencing late effects, 61% were extremely/very worried about late effects. Those who felt their child was at high risk of experiencing late effects were more likely to worry (OR = 4.7, P = 0.02). CONCLUSIONS: Many parents feel inadequately informed about late effects of cancer treatment, and only one-fifth of parents consider late effects to be likely for their child. However, a majority of parents worry about late effects, including ones they think their child is unlikely to experience. Although some worry is anticipated, disproportionate worry may be mitigated by addressing both educational shortfalls and emotional concerns.

Disparities in pediatric psychosocial oncology utilization.

BACKGROUND: Integratedbehavioral health models have been proposed as care delivery approaches to mitigate mental health disparities in primary care settings. However, these models have not yet been widely adopted or evaluated in pediatric oncology medical homes. METHODS: We conducted a retrospective cohort study of 394 children with newly diagnosed cancer at Dana-Farber/Boston Children's Cancer and Blood Disorders Center (DF/BCH) from April 2013 to January 2017. Baseline sociodemographic characteristics and psychiatry utilization outcomes at 12 months following diagnosis were abstracted from the medical record. The severity of household material hardship (HMH), a concrete poverty exposure, at diagnosis and race/ethnicity were characterized by parent report using the Psychosocial Assessment Tool 2.0 (PAT). Associations between sociodemographic characteristics and receipt of psychiatry consultation were assessed with multivariable logistic regression models. RESULTS: Among 394 children, 29% received a psychiatric consultation within 12 months postdiagnosis. Of these, 88% received a new psychiatric diagnosis, 76% received a psychopharmacologic recommendation, and 62% received a new behavioral intervention recommendation. In multivariable logistic regression adjusting for age, cancer diagnosis, and PAT total score, there was no statistically significant association between HMH severity or household income and psychiatry utilization. Children who identified as racial/ethnic minorities were significantly less likely to receive a psychiatry consultation (OR = 0.48, 95% CI = 0.27-0.84). CONCLUSIONS: In a pediatric oncology medical home with an integrated behavioral health model, socioeconomic status was not associated with disparate psychiatry utilization. However, there remained a profound racial/ethnic disparity in psychiatry utilization, highlighting the need for additional research and care delivery intervention.

Pyruvate kinase deficiency in children.

BACKGROUND: Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management. METHODS: An international, multicenter registry enrolled 124 individuals younger than 18 years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected. RESULTS: There was a wide range in the age at diagnosis from 0 to 16 years. Presentation in the newborn period ranged from asymptomatic to neonatal jaundice to fulminant presentations of fetal distress, myocardial depression, and/or liver failure. Children <5 years old were significantly more likely to be transfused than children >12 to <18 years (53% vs. 14%, p = .0006), which correlated with the timing of splenectomy. Regular transfusions were most common in children with two severe PKLR variants. In regularly transfused children, the nadir hemoglobin goal varied considerably. Impact on quality of life was a common reason for treatment with regular blood transfusions and splenectomy. Splenectomy increased the hemoglobin and decreased transfusion burden in most children but was associated with infection or sepsis (12%) and thrombosis (1.3%) even during childhood. Complication rates were high, including iron overload (48%), perinatal complications (31%), and gallstones (20%). CONCLUSIONS: There is a high burden of disease in children with PKD, with wide practice variation in monitoring and treatment. Clinicians must recognize the spectrum of the manifestations of PKD for early diagnostic testing, close monitoring, and management to avoid serious complications in childhood.

Comparison of Outcomes of Myeloablative Allogeneic Stem Cell Transplantation for Pediatric Patients with Bone Marrow Failure, Myelodysplastic Syndrome and Acute Myeloid Leukemia with and without Germline GATA2 Mutations.

Germline mutations in GATA2 are associated with an inherited predisposition to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) remains the only curative therapy. However, patients may be at an increased risk for transplant-related toxicity (TRT) and transplant-related mortality (TRM) due to their underlying disease biology. We performed a retrospective case-control study of pediatric patients with BMF/MDS/AML with germline GATA2 mutations, comparing HSCT outcomes to randomly selected patients without germline GATA2 mutations and BMF/MDS (control A) and acute leukemia (control B). The 5-year overall and disease-free survival rates in the GATA2 cohort (65%, 51%) were similar to control A (58%, 49%) and B (45%, 43%) cohorts. In contrast, the 5-year event-free survival rate was significantly lower in the GATA2 cohort (7% ± 6%, 28% ± 10%, and 33% ± 8% for GATA2, A, and B, respectively), due to an increased number of unique TRTs. Specifically, neurologic toxicities occurred significantly more frequently in GATA2 patients than in the control groups, and post-HSCT thrombotic events occurred only in the GATA2 cohort. There was no difference in TRM, infections, or graft-versus-host disease across groups. The higher incidence of thrombotic and neurologic events specific to GATA2 patients warrants further investigation and has potential treatment ramifications.

Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study.

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin (P = .007), lower indirect bilirubin (P = .005), and missense PKLR mutations (P = .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480.

Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency.

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.

Risk Factors and Outcomes of Nonmelanoma Skin Cancer in Children and Young Adults.

OBJECTIVE: To identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children. STUDY DESIGN: This was a multicenter, retrospective, case-control study of patients <20 years of age diagnosed with NMSC between 1995 and 2015 from 11 academic medical centers. The primary outcome measure was frequency of cases and controls with predisposing genetic conditions and/or iatrogenic exposures, including chemotherapy, radiation, systemic immunosuppression, and voriconazole. RESULTS: Of the 124 children with NMSC (40 with basal cell carcinoma, 90 with squamous cell carcinoma), 70% had at least 1 identifiable risk factor. Forty-four percent of the cases had a predisposing genetic condition or skin lesion, and 29% had 1 or more iatrogenic exposures of prolonged immunosuppression, radiation therapy, chemotherapy, and/or voriconazole use. Prolonged immunosuppression and voriconazole use were associated with squamous cell carcinoma occurrence (cases vs controls; 30% vs 0%, P = .0002, and 15% vs 0%, P = .03, respectively), and radiation therapy and chemotherapy were associated with basal cell carcinoma occurrence (both 20% vs 1%, P < .0001). Forty-eight percent of initial skin cancers had been present for >12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001). CONCLUSIONS: NMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management.

The relationship between household income and patient-reported symptom distress and quality of life in children with advanced cancer: A report from the PediQUEST study.

BACKGROUND: Children with advanced cancer experience high symptom distress, which negatively impacts their health-related quality of life (HRQOL). To the authors' knowledge, the relationship between income and symptom distress and HRQOL is not well described. METHODS: The Pediatric Quality of Life and Symptoms Technology (PediQUEST) multisite clinical trial evaluated an electronic patient-reported outcome system to describe symptom distress and HRQOL in children with advanced cancer via repeated surveys. The authors performed a secondary analysis of PediQUEST data for those children with available parent-reported household income (dichotomized at 200% of the Federal Poverty Level and categorized as low income [<$50,000/year] or high income [≥$50,000/year]). The prevalence of the 5 most commonly reported physical and psychological symptoms was compared between groups. Multivariable generalized estimating equation models were used to test the association between household income and symptom distress and HRQOL. RESULTS: A total of 78 children were included in the analyses: 56 (72%) in the high-income group and 22 (28%) in the low-income group. Low-income children were more likely to report pain than high-income children (64% vs 42%; P=.02). In multivariable models, children from low-income families demonstrated a uniform trend toward higher total (ßlow-high =3.1; 95% confidence interval [95% CI], -0.08 to 6.2 [P=.06]), physical (ß=3.8; 95% CI, -0.4 to 8.0 [P=.09]), and psychological (ß=3.46; 95% CI, -1.91 to 8.84 [P=.21]) symptom distress compared with children from high-income families. Low income was associated with a uniform trend toward lower total (ß=-7.9; 95% CI, -14.8, to -1.1 [P=.03]), physical (ß=-11.2; 95% CI, -21.2 to -1.2 [P=.04]), emotional (ß=-5.8; 95% CI, -13.6 to 2.0 [P=.15]), social (ß=-2.52; 95% CI, -9.27 to 4.24 [P=.47]), and school (ß=-9.8; 95% CI, -17.8 to -1.8 [P=.03]) HRQOL. CONCLUSIONS: In this cohort of children with advanced cancer, children from low-income families were found to experience higher symptom burden and worse QOL.

Household material hardship in families of children post-chemotherapy.

Poverty is an important patient-reported outcome of therapy and a potential predictor of outcome disparities in pediatric cancer. We previously identified that nearly 30% of pediatric cancer families experience household material hardship (HMH), a concrete measure of poverty including food, energy, or housing insecurity, during the first 6 months of chemotherapy. We conducted a follow-up survey in a subcohort of these families at least 1 year off-therapy and found that 32% reported HMH in early survivorship. Persistently high concrete resource needs off-therapy may have significance for child health and quality of life, and thus represent targets for future investigation.

Influence of early phase clinical trial enrollment on patterns of end-of-life care for children with advanced cancer.

We conducted a retrospective cohort study of 125 pediatric oncology patients who died in 2010-2014 to explore how healthcare utilization, pediatric palliative care (PPC) receipt, and end-of-life care (EOLC) differed between patients enrolled in early phase clinical trials (EP) and those not enrolled (NEP). Baseline characteristics and healthcare utilization did not significantly differ between groups. EP patients received PPC consultation closer to death than NEP patients (median days before death = 58 [interquartile range = 16-84] vs. 85 [32-173]; P = 0.04). Our findings suggest that early phase trial enrollment does not substantially alter EOLC for children with advanced cancer but may contribute to later PPC engagement. Future studies should definitively assess the relationship between trial enrollment and PPC timing.

Correction to: A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions.

The published online version contains mistake in Acknowledgment Section. The author name "Steve Gorin, M.D." should have been "Steven Gorin, D.O, M.S.Ed.".

Rethinking childhood ependymoma: a retrospective, multi-center analysis reveals poor long-term overall survival.

Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Chicago's Ann & Robert H. Lurie Children's Hospital between 1985 and 2008, and an additional 360 ependymoma patients identified from the Surveillance Epidemiology and End Results (SEER) database. For the institutional cohort, we evaluated clinical and histopathological prognostic factors of overall survival (OS) and progression-free survival (PFS) using the log-rank test, and univariate and multivariate Cox proportional-hazards models. Overall survival rates were compared to those of the SEER cohort. Median follow-up time was 11 years. Ten-year OS and PFS were 50 ± 5% and 29 ± 5%, respectively. Findings were validated in the independent SEER cohort, with 10-year OS rates of 52 ± 3%. GTR and grade II pathology were associated with significantly improved OS. However, GTR was not curative for all children. Ten-year OS for patients treated with a GTR was 61 ± 7% and PFS was 36 ± 6%. Pathological examination confirmed most recurrent tumors to be ependymoma, and 74% occurred at the primary tumor site. Current treatment paradigms are not sufficient to provide long-term cure for children with ependymoma. Our findings highlight the urgent need to develop novel treatment approaches for this devastating disease.

A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions.

INTRODUCTION: The purpose of the present investigation is to report on detailed complications among a much larger group of 2372 orthopaedic patients treated with stem cell injections who were followed in a treatment registry for up to nine years. METHODS: All patients underwent an MSC-based, percutaneous injection treatment of an orthopaedic condition between December 2005 and September 2014 at one of 18 clinical facilities. Treated areas of the body included the knee, hip, ankle/foot, hand/wrist, elbow, shoulder, and spine. The patients were followed prospectively via enrollment in a treatment registry. Patients were followed prospectively at one, three, six and 12 months, and annually thereafter, using an electronic system, ClinCapture software. RESULTS: A total of 3012 procedures were performed on 2372 patients with follow-up period of 2.2 years. A total of 325 adverse events were reported. The majority were pain post-procedure (n = 93, 3.9 % of the study population) and pain due to progressive degenerative joint disease (n = 90, 3.8 % of the study population). Seven cases reported neoplasms, a lower rate than in the general population. The lowest rate of adverse events was observed among patients injected with BMC alone. CONCLUSION: Lowest rate of adverse events was among those patients receiving BMC injections alone, but the higher rate of AEs for BMC plus adipose and cultured cells was readily explained by the nature of the therapy or the longer follow-up. There was no clinical evidence to suggest that treatment with MSCs of any type in this study increased the risk of neoplasm.

A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis.

BACKGROUND: Prior studies describing the treatment of symptomatic knee osteoarthritis with injections of bone marrow concentrate have provided encouraging results. The relationship between the cellular dose contained within the bone marrow concentrate and efficacy of the treatment, however, is unclear. In the present study we describe clinical outcomes for symptomatic knee osteoarthritis in relation to higher and lower cell concentrations contained within a bone marrow concentrate treatment protocol. METHODS: Data from an ongoing patient registry was culled to identify 373 patients that received bone marrow concentrate injections for the treatment of 424 osteoarthritic knee joints. The clinical scales for these patients were assessed at baseline and then tracked post-procedure at 1, 3, 6 and 12 months, and annually thereafter. Tracked outcomes included the numeric pain scale; a lower extremity functional questionnaire; an International Knee Documentation Committee scale; and a subjective improvement rating scale. Using pain and functional outcome measures, a receiver operating characteristic analysis was used to define an optimal clinical outcome threshold at which bone marrow nucleated cell count could be divided into either a lower or higher cell count group within a treatment protocol. RESULTS: The lower and higher cell count groups were defined using a threshold of 4 × 10(8) cells. There were 224 and 185 knee joints treated in the lower (≤4 × 10(8)) and higher (>4 × 10(8)) cell count groups respectively. Most joints were diagnosed with early stage knee osteoarthritis. Both the lower and higher cell count groups demonstrated significant positive results with the treatment for all of the pain and functional metrics. The higher cell count group reported lower post treatment numeric pain scale values, in comparison with the lower cell count group (1.6 vs. 3.2; P < 0.001). No significant differences were detected for the other metrics, however. CONCLUSIONS: Improved function and reduced pain was observed in patients treated with a bone marrow concentrate protocol regardless of cellular dose; however, patients receiving a higher concentration of cells reported a better pain outcome in comparison with the lower dose group. These preliminary findings suggest that cell dose may be an important factor governing clinical outcomes in autologous bone marrow concentrate treatment of knee osteoarthritis. Further studies using a larger patient population may help elucidate these findings.