The Sigmoid Colon as an Unusual Primary Site of T Cell Lymphoma in a Patient Presenting With Brain Metastasis.

Intestinal T-cell lymphomas are an uncommon type of gastrointestinal malignancy, primarily found in the stomach and small bowel. The liver represents the most common distant organ for metastasis in gastrointestinal malignancies, followed by the lungs. Brain and muscular metastases are rare. We present intestinal T-cell lymphoma with a primary site in the sigmoid colon and metastasis to the brain, meninges, and psoas muscle. Biopsy of the malignant mass confirmed intestinal T-cell lymphoma. To our knowledge, this is the first colon T-cell lymphoma with primary brain and meningeal metastasis with another uncommon site of muscular metastasis.

Myeloid madness: assessing diagnostic inconsistency between the new WHO and ICC schemes for myelodysplastic/myeloproliferative neoplasms.

The classification of haematological neoplasms recently underwent revision, generating two separate schemes-the International Consensus Classification and the fifth edition of the WHO classification. The new division into separate classification systems presents challenges for haematopathologists, haematologists/oncologists and patients. While it is too early to assess the full clinical impact, we sought to identify diagnostic discordance which may arise from applying separate classification schemes in myeloid neoplasia, and particularly in the challenging category of myelodysplastic syndrome/myeloproliferative neoplasms. A review of 64 such cases found 1 case with a significant discrepancy between the WHO and International Consensus Classification systems, and 9 cases with nominal discrepancies. Confusion from the use of conflicting diagnostic terms represents a potential source of patient harm, increased pathologist workload and burnout and erosion of clinician and patient trust.

Therapy-related B-lymphoblastic leukemia after multiple myeloma.

New therapies for multiple myeloma have improved outcomes, but are associated with therapy-related hematologic malignancies. We report eight patients with therapy-related B-lymphoblastic leukemias (t-B-ALL) in the setting of therapy for multiple myeloma, which included lenalidomide maintenance. A subset of patients had pancytopenia and low-level marrow involvement by acute leukemia, an unusual finding in de novo B-ALL. One patient died of chemotherapy complications; the other seven responded. No patient died of B-ALL (median follow up of 1.0 years). Our series suggests that t-B-ALL is clonally unrelated to myeloma, presents with diverse cytogenetic abnormalities, and responds well to B-ALL therapy.

Favorable outcomes of acute leukemias of ambiguous lineage treated with hyperCVAD: a multi-center retrospective study.

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Twenty-five patients were identified, including 23 with mixed phenotype acute leukemia (MPAL) and two with acute undifferentiated leukemia. Five of 8 tested (63%) had FLT3-ITD and 3 of 25 (12%) were Philadelphia chromosome-positive. The complete remission (CR) rate was 76%, with CR with incomplete count recovery (CRi) in an additional 8%, for an overall response rate of 84%. Median number of cycles to CR/CRi was 1. There were no deaths in the first 30 days. Of the 21 patients achieving CR or CRi, 14 (66%) proceeded to allogeneic hematopoietic stem cell transplantation. With a median follow-up time of 31.6 months, median overall survival for the entire cohort was not reached, and the estimated 2-year survival was 63%. HyperCVAD can be considered an effective and tolerable front-line regimen for patients with ALAL, and warrants further prospective study.

The Performance of Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

OBJECTIVE: The diagnostic criteria for secondary hemophagocytic lymphohistiocytosis (HLH) have not been validated in the critically ill adult population. We set out to evaluate the performance of diagnostic criteria and determine the ferritin cutoff in critically ill adults. DESIGN: A retrospective single-center study. SETTING AND PATIENTS: Patients admitted to intensive care unit between 2008 and March 2010. Data were collected on consecutive patients who had ferritin measured. Charts were reviewed for the diagnostic criteria of HLH and components of Hscore. MEASUREMENTS AND MAIN RESULTS: A total of 445 patients had a ferritin level measured during the study period. A diagnosis of HLH was made for 10 patients. Having 5 of 6 criteria had a specificity of 97% and a sensitivity of 70%. Hemophagocytosis was found in 41 (47.1%) of 87 bone marrow biopsies. Two hundred thirty-one patients had a ferritin level above 500 ng/dL. When determining the odds of HLH being clinically diagnosed, the optimal cut point for ferritin was 1197 ng/dL. When determining the odds of HLH based on the Hscore, the best cutoff was 143.5 (sensitivity of 90% and specificity of 90%) and patients who had HLH in our study population had an Hscore of 203.8 ± 64.9. CONCLUSION: In this cohort of critically ill patients, the HLH criteria are specific for HLH but not sensitive. Critically ill patients can have a higher incidence of hemophagocytosis without HLH. A higher ferritin cutoff in combination with 5 other clinical criteria is comparable to the Hscore for the recognition of HLH in the critically ill population.

Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia.

The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB-RC) was calculated for treatment-naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB-RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24-2·64, P < 0·005). PBB-RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27-3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52-0·87]. African American patients had poorer OS adjusted for PBB-RC (HR = 2·18; 95% CI: 1·13-4·23), while race was not associated with D14BM or CR rate. PBB-RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML.

Relapsed Philadelphia Chromosome-Positive Pre-B-ALL after CD19-Directed CAR-T Cell Therapy Successfully Treated with Combination of Blinatumomab and Ponatinib.

Adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with conventional chemotherapy have dismal outcomes. Novel immunotherapies targeting CD19, including the bispecific T-cell engager blinatumomab and chimeric antigen-receptor T (CAR-T) cells, have revolutionized the treatment of R/R B-ALL. Robust response rates to CAR-T cell therapy after blinatumomab have recently been reported, but it is unknown whether blinatumomab can be effective following failure of anti-CD19 CAR-T cell therapy. Herein, we describe a patient with Philadelphia chromosome-positive B-ALL who relapsed after CD19-directed CAR-T therapy, but subsequently responded to the combination of blinatumomab and the tyrosine kinase inhibitor ponatinib, with the achievement of a complete remission lasting 12 months.