Therapy-related Acute Myeloid Leukemia in Non-Hodgkin Lymphoma Survivors: Risk, Survival Outcomes and Prognostic Factor Analysis.

BACKGROUND: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. This extensive database study aims to quantify the risk of tAML in NHL and determine the impact of tAML on the overall survival (OS) of patients with NHL. MATERIALS AND METHODS: Patients diagnosed with NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results database. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software were used to calculate SIR and the absolute excess risk of tAML. Overall survival (OS) was evaluated using Kaplan-Meier curves and compared using log-rank tests. Multivariate analysis was used to study the role of each covariate on OS in patients with tAML. RESULTS: The SIR of tAML was 4.89 (95% CI 4.41-5.41), with a higher incidence of tAML observed for age <60 years, NHL prior to 2013 and within 5 years of diagnosis, and those who received chemotherapy. NHL patients with tAML had lower OS than those without tAML (5-year OS 59% vs. 13%, p < 0.001). Patients with tAML showed worse OS than de novo AML in univariate analysis (5-year OS 13% vs. 25%, p = 0.001) but not in multivariate analysis (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years and lack of chemotherapy were associated with poor OS in tAML subcategory. CONCLUSION: Age, time since NHL diagnosis, and receipt of chemotherapy directly influence the risk of development of tAML in NHL survivors.

Acquired elliptocytosis in chronic myeloid neoplasms: An enigmatic relationship to acquired red cell membrane protein and genetic abnormalities.

Nineteen reports of 41 cases of acquired red cell elliptocytosis associated with a chronic myeloid neoplasm are described. Although the majority of cases have an abnormality of the long arm of chromosome 20, del(q20), several cases do not. Moreover, in one case a specific qualitative abnormality of red cell protein band 4.1(4.1R) was reported; however, several subsequent cases could find no abnormality of a red cell membrane protein or found a different abnormality, usually quantitative. Thus, this striking red cell phenotypic feature, acquired elliptocytosis, seen in myelodysplastic syndrome and other chronic myeloproliferative diseases, closely simulating the red cell phenotype of hereditary elliptocytosis, has an unexplained genetic basis, presumably as the result of an acquired mutation(s) in some chronic myeloid neoplasms.

Massive splenomegaly in hairy cell leukemia causing urinary retention.

Hairy cell leukemia can cause massive splenomegaly which may lead to urinary retention and constipation. Patients usually require a splenectomy for relief of symptoms.

Hepatosplenic T-Cell Lymphoma in an Immunocompetent Young Male: A Challenging Diagnosis.

Hepatosplenic T-cell lymphoma is a rare but highly aggressive form of T-cell malignancy. As cases are not routinely seen in practice, the malignancy can be confused with other hematologic conditions that have a similar presentation. Here in, we present the challenges faced in diagnosing a 27-year-old-male who initially presented with asymptomatic pancytopenia and then developed massive splenomegaly over the next three months. After an elaborate workup, including a bone marrow biopsy and extensive serological testing, which all turned out to be negative, he eventually underwent a splenectomy with biopsy results confirming hepatosplenic T-cell lymphoma.

Acute Myocardial Infarction as Initial Manifestation of Acute Myeloid Leukemia: A Rare Manifestation of Leukostasis.

Leukostasis is a medical emergency caused by compromise of tissue perfusion secondary to hyperleukocytosis in acute myeloid leukemia (AML). Typically it affects lungs and brain, with cardiac involvement being exceedingly rare. We present a case of AML presenting as acute coronary syndrome secondary to leukostasis-induced myocardial ischemia. A 43-year-old morbidly obese gentleman presented with typical anginal chest pain. On examination, he was diaphoretic and in acute distress secondary to pain. EKG revealed ST elevation in lead I and aVL and PR depressions in precordial leads. Troponin peaked at 5.55 ng/mL. Echocardiogram showed normal left ventricle function with no wall motion abnormality. Blood work was notable for white blood cell (WBC) count of 185,200 cells/µL with 81% blasts. Coronary angiogram revealed no obstruction. Emergent leukapheresis and hydroxyurea were initiated. WBC count decreased to 48,200 cells/ µL and angina resolved after leukapheresis. With diagnosis of AML, he received 7+3 induction chemotherapy with cytarabine and idarubicin, followed by re-induction and consolidation chemotherapy. He subsequently underwent allogenic bone marrow transplantation and achieved complete remission. Hyperleukocytosis in AML can cause leukostasis, characterized by evidence of tissue ischemia. Coronary vasculature accounts for 6% of cases with leukostasis. This can manifest as myocardial infarction. Emergent and timely initiation of leukapheresis can potentially lead to a complete resolution of microvascular occlusion.

The scope and value of an anticoagulation stewardship program at a community teaching hospital.

To report the impact of an inpatient anticoagulation stewardship program at a community hospital to promote optimal anticoagulant use. The anticoagulation team (ACT) stewardship program consists of two clinical pharmacists and hematologists to provide oversight of anticoagulants, high cost reversal agents including prothrombin complex concentrate (PCC, Kcentra™), and heparin-induced thrombocytopenia (HIT) management. Intervention data and number of charts reviewed were collected. Average cost avoidance data was applied to ACT interventions to estimate cost savings. The PCC analysis was conducted via retrospective chart review during the pre-intervention period. Prospective monitoring continued in the post-intervention period to determine the percentage of PCC use within the institution's guidelines or approved by ACT or hematology. A total of 19,445 patient charts were reviewed, and 1930 (10%) contained stewardship opportunity. Of the interventions, 71% were provided to the medical service and 22% to surgical services with acceptance rates of 91 and 83%, respectively. Intervention cost-avoidance calculated to be $694,217. Regarding HIT interventions, 52% of interventions involved pharmacokinetic/pharmacodynamics optimization in 18 patients with suspected or confirmed HIT. Regarding PCC use, 55.8% of PCC orders were considered inappropriate in the pre-invention period versus 2.6% post-intervention. Appropriate PCC doses per month post-intervention were consistent with pre-intervention doses (7.67 vs. 6.73, respectively). The projected annual PCC cost savings is $385,473. The overall estimated financial impact of ACT is $799,690 saved. Implementation of an anticoagulation stewardship program reduced costs and improved clinical outcomes. It is also expected that anticoagulant optimization and provider education improved overall safety.

Pathology of thrombotic thrombocytopenic purpura in the placenta, with emphasis on the snowman sign.

Thrombotic thrombocytopenic purpura (TTP) commonly affects women of childbearing age. Although cases of TTP in pregnancy have been reported, the pathology of TTP in the placenta has not been described. In other organs, TTP has a distinctive pathology of arteriolar aneurysms with segmental intramural hyaline deposits. Published many decades ago, these classic papers antedate modern computerized literature searches, so this information has not been included in many modern reviews on TTP. We report 2 cases of TTP in pregnancy, both leading to fetal loss in the 2nd trimester. We noticed a distinctive pathology of TTP in the spiral arteries on the maternal surface of the placenta, particularly the "snowman sign," which differs somewhat from TTP in other organs due to the fact that TTP is superimposed on trophoblast-induced changes in these spiral arteries. In one of our cases, where the clinical diagnosis of TTP was difficult, the distinctive placental findings helped reinforce the clinical decision to perform potentially life-saving plasmapheresis.

Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features.

Hereditary hemochromatosis is a common disorder of iron metabolism most frequently associated with mutations in the HFE gene. Hereditary hemochromatosis may be caused by other less common genetic mutations including those in the ferroportin gene. Whereas hereditary hemochromatosis associated with HFE mutations is an autosomal recessive disorder, essentially all cases of hereditary hemochromatosis associated with ferroportin mutations follow an autosomal dominant pattern of inheritance, and most cases are notable for the lack of an elevated transferrin saturation and presence of iron deposition in Kupffer cells. This report describes the clinical and laboratory features of a family with hereditary hemochromatosis associated with a previously unrecognized ferroportin mutation (Cys326Ser). Three generations of the family are described. The disease in this family is notable for young age at onset, elevated transferrin saturation values, and hepatocyte iron deposition. The distinct molecular and clinical features reflect the heterogeneous nature of this disease.

Treatment of acute promyelocytic leukemia in the very elderly: case report and review of the literature.

Acute promyelocytic leukemia (APL) is the most curable subtype of AML yet it is not known to what extent newer therapies will succeed in the very elderly. Conventional chemotherapeutic induction regimens are usually too toxic for older patients, however, all trans-retinoic acid (ATRA) and arsenic trioxide (ATO) may be useful therapeutic options if used judiciously. This case series describes three octogenarians with APL all treated with ATRA and achieved complete remissions. The last patient received ATO at the time of first relapse and achieved a second remission. To our knowledge, this is the first report of successful use of ATO for induction in an octogenarian with APL.

Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients.

Two HFE gene mutations, C282Y and H63D, underlie the vast majority of cases of hereditary hemochromatosis. We performed a cross-sectional primary care-based study to determine the allele frequency of the C282Y and H63D mutations and the penetrance of each of the affected genotypes defined by their presence. Patients had previously undergone transferrin saturation (TS) testing. A total of 4865 unselected frozen serum samples were analyzed to determine serum ferritin (SF) levels. Genomic DNA isolated from these samples was analyzed for the C282Y and H63D HFE mutations. Homozygotes for each mutation and compound heterozygotes were evaluated to determine clinical penetrance. The allele frequency of C282Y was 0.0507 among Caucasian and 0.0067 among African Americans; that of H63D was 0.1512 and 0.0263, respectively. TS was > or =55% in 83% of individuals with C282Y/C282Y, 14.5% of C282Y/H63D, and 5% of H63D/H63D; SF was > or =300 microG/L in 42, 9, and 5% of these genotypes, respectively. None of the 12 C282Y homozygotes had cardiac dysfunction or hepatic cirrhosis. Only 9/129 (7%) individuals with the genotypes C282Y/H63D or H63D/H63D had a SF > or =300 microG/L; many had explanations other than iron overload that accounted for this increase. Thus, the prevalence of the common HFE mutations is the same in our population as previously described. TS screening would detect most C282Y homozygotes but not the other two genotypes. The penetrance of C282Y/C282Y is significant. The biochemical penetrance of H63D/H63D and C282Y/H63D is modest and the clinical penetrance is low.