A Case of JAK2V617F-Negative Myeloproliferative Neoplasm in a Young Female Presenting With Extreme Thrombocytosis.

Thrombocytosis is a commonly observed condition in clinical practice and typically results from various pathophysiological factors, such as iron deficiency, blood loss, infection, medications, rheumatologic conditions, malignancy, asplenia, post-splenectomy, or familial factors. However, extreme thrombocytosis, defined as a platelet count > 10,000 K/UL (equal or greater than a million), is a rare occurrence. In this report, we present a compelling case of severe thrombocytosis attributed to underlying chronic myelogenous leukemia (CML), further complicated by coexisting iron deficiency. It is essential to emphasize that not all instances of extreme thrombocytosis are indicative of essential thrombocythemia. Hence, maintaining a high level of suspicion for non-ET myeloproliferative neoplasms (MPNs) such as CML, as well as other underlying conditions like iron deficiency anemia, is crucial for accurate diagnosis and timely management.

COVID-19-associated thrombotic angiopathy improved after plasma exchange.

Utilization of therapeutic plasma exchange in select patients with COVID-19 microangiopathy may provide useful treatment by modulation of inflammatory cytokines and coagulation cascade to maintain homeostasis.

Patterns of leukocyte recovery predict infectious complications after CD19 CAR-T cell therapy in a real-world setting.

BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. METHODS: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. RESULTS: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months). CONCLUSIONS: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.

Axicabtagene ciloleucel CD19 CAR-T cell therapy results in high rates of systemic and neurologic remissions in ten patients with refractory large B cell lymphoma including two with HIV and viral hepatitis.

Axicabtagene ciloleucel (Axi-cel) is a CD-19 Chimeric Antigen Receptor T cell therapy approved for the treatment of relapsed/refractory diffuse large B cell lymphoma. We treated ten patients with DLBCL post-FDA approval in an inner-city tertiary center in the Bronx. Eight patients (80%) had received ≥ 3 lines of therapy, six patients had received prior radiation, and seven had recurrent disease after prior autologous hematopoietic stem cell transplant (AHCT). Our cohort included one patient with HIV, two patients with hepatitis B, and two patients with CNS involvement of lymphoma. Axi-cel treatment led to significant responses with 8/10 patients achieving a complete remission at 3 months, including both patients with prior CNS involvement. The treatment was generally well tolerated with 20% of patients experiencing grade ≥ 2 CRS. One patient each with HIV and hepatitis B responded without significant toxicities. In conclusion, Axi-cel led to significant efficacy with manageable toxicity in DLBCL in a real-world setting.

Twist of Fate for Acute Promyelocytic Leukemia: TRIB3-TWIST1 Interaction Promotes Resistance.

While acute promyelocytic leukemia has a good prognosis with all-trans retinoic acid (ATRA) treatment, ATRA resistance is a major obstacle. It is now demonstrated that TRIBBLES 3 (TRIB3) stabilizes TWIST1, leading to ATRA resistance. Peptides that disrupt this interaction lead to the degradation of TWIST1 and overcome ATRA resistance.See related article by Lin et al., p. 6228.