Cancer In The National Cancer Institute Inherited Bone Marrow Failure Syndrome Cohort After Fifteen Years Of Follow-Up

This study aimed to describe the incidence and characteristics of malignancy in patients with inherited bone marrow failure syndromes over a fifteen year duration. This was a prospective cohort study conducted by the National Cancer Institute. The Inherited Bone Marrow Syndrome Cohort was opened in Jan 2002 and continues to accrue participants. This cohort enrolled patients with Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome.
Patients (n=530) were enrolled in the cohort starting in 2002 with the aforementioned diagnoses of inherited bone marrow failure syndromes. Diagnosis was confirmed at the NCI. Demographic and outcome measures were then collected by parent/patient report and medical chart review. The ratio of expected to observed malignancy rates were calculated and adjusted for age, sex, race, and birth cohort.
Overall leukaemia was diagnosed at an incidence of 3% with DC, FA and SDS and 0% in the cohort with DBA. DC, FA and SDS had an increased risk of ALL and AML, but odds ratios were higher for AML. Solid tumours were diagnosed at an incidence of 5% DBA, 7% DC, 12% FA and 3% SDS. The cumulative incidence of solid tumors was close to 20% by age 65 in both DC and FA.
HSCT drastically left shifted the age of diagnosis of malignancy and increased the chances of secondary malignancy in FA (rate ratio 3.5) and DC (rate ratio 5).
For Fanconi Anemia patients developed head and neck squamous cell carcinomas (HNSCC), AML, vulvar SCC and brain tumors. For DC, patients reported HNSCC, AML and NHL. In DBA, patients developed lung, colon and cervical cancers. The SDS cohort was very small (n= 35) and there were two diagnoses of AML and cervical cancer.
The increased risk of both leukemias and solid tumors in all diagnostic groups were statistically significant.
This study was descriptive and therefore inferences cannot be made about the underlying causality of cancer predisposition in these syndromes. There was no analysis based on the genotype to cancer predisposition.
There could have been an enrolment bias in this study, with patients with more severe disease course being more likely to agree to participate.
This is the largest cohort study in terms of patient life years (enrolment and duration of study) to describe outcomes in inherited bone marrow failure syndromes. Patients with inherited bone marrow failure syndromes are at increased risk for leukemias and solid tumors. This risk is greatly increased and left shift (in terms of age of diagnosis) by bone marrow transplant, which is consistent with previously reported literature.
The specific types of malignancies are specific to the bone marrow failure syndrome and are described in this article. This is relevant to clinical practice in terms of surveillance of this patient population.

Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

This is review with recommendations for platelet transfusions in oncology patients (adult and pediatric).

Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer

The Childhood Cancer Survivor Study (CCSS) led to the largest cancer survivor follow-up cohort. It is based on data extracted from medical records and questionnaires that were sent to childhood cancer survivors (CCS). CCS have been shown to have a >10-fold increased risk of ischemic heart disease and stroke compared with siblings. This study developed a risk-prediction model using end-of-treatment data to risk stratify CCS and externally validate the model.
This manuscript used data from the CCSS from children diagnosed between 1970 and 1986 at 26 institutions in the United States and Canada (n=13,060). A random sample of siblings (n=4,023) served as comparison cohort. Two validation datasets were used: the SJLIFE cohort from St. Jude Children’s Research Hospital (led by the same team as the CCSS cohort) and the EKZ/ AMC cohort (unrelated group, n= 1,300 - 1,800 CCS). A set of variables with demographic and treatment data were tested for their association with ischemic heart disease and stroke.
Predictors of ischemic heart disease were male sex, neck or chest radiation; predictors for stroke were alkylator therapy, platinum agents, cranial and chest radiation. Two models were created: a simple model where cancer therapy–related exposures were categorized as yes or no only; and a standard model where clinical dose information was known. Risk scores were attributed and summed to create low-, moderate-, and high-risk groups. Low-risk groups had cumulative incidence risks of =15% of ischemic heart disease or stroke, respectively.
The cohorts used in this study were diagnosed three or more decades ago (training data set) or at least 15 years ago (validation data sets). Therefore, these findings might not be valid for modern treatment protocols. Particularly radiation was greatly reduced and application techniques changed within the last decades.
This study quantified risk factors for ischemic heart disease and stroke after childhood cancer treatment and compiled a prediction tool which might help estimate the risk for CCS (https://ccss.stjude.org/tools-and-documents/calculators-and-other-tools/ccss-cardiovascular-risk-calculator.html).