Partial response to venetoclax and ruxolitinib combination in a case of refractory T-prolymphocytic leukemia.

Background: T-prolymphocytic leukemia (T-PLL) is an aggressive hematologic malignancy. A portion of patients can be cured with alemtuzumab induction followed by allogeneic hematopoietic stem cell transplant, but patients who relapse after transplant have a poor prognosis, and there is no standard of care.Methods: We report a case of a 64-year-old man with relapsed JAK3-mutant T-PLL following allogeneic transplant who was treated with ruxolitinib and venetoclax.Results: Treatment with ruxolitinib and venetoclax resulted in a partial response including stabilization of the peripheral lymphocyte count, improvement in thrombocytopenia, decrease in splenomegaly, and a numerical reduction in the percentage of bone marrow involved by T-PLL. The combination was well tolerated with the exception of neutropenic infections.Conclusion: This case adds to the growing body of literature supporting venetoclax and rituximab as a viable treatment option for relapsed/refractory T-PLL with JAK-STAT alterations.

Clinicopathologic Features and Treatment of CD10-Positive Mantle Cell Lymphoma: A Case Report and Review of Literature.

Mantle cell lymphoma (MCL) is a rare and aggressive non-Hodgkin's B cell lymphoma characterized by the translocation t(11;14) (q13;32) and overexpression of CCND1. MCL is immunophenotypically identified as CD20+, CD5+, CyclinD1+, CD43+, CD10-, BCL6-, and CD23-. It is often distinguished from B cell lymphomas of germinal center cell origin by the absence of CD10 expression. Here we report the unique clinicopathologic features of a patient with CD10+ MCL with gastrointestinal involvement and review current literature identifying this unique immunophenotype.

Successful Treatment of Autoimmune Hemolytic Anemia Concomitant with Proliferation of Epstein-Barr Virus in a Post-Heart Transplant Patient.

Autoimmune hemolytic anemia (AIHA) is a rare complication following heart transplantation and has been attributed to several etiologies including infections, immunosuppressive medications, and post-transplant lymphoproliferative disorders. We report a 23-year-old male presenting 22 years after heart transplantation with severe AIHA. Laboratory findings were notable for positive IgG autoantibody against RBCs and high titer Epstein-Barr virus (EBV) viremia. Shortly after the first unit of irradiated RBC transfusion and high dose steroids, the patient developed acute dyspnea and hypoxia requiring intubation. Further workup demonstrated that the patient had Methicillin-sensitive Staphylococcus aureus (MSSA) pneumonia (PNA) and bacteremia, requiring antibiotics. Patient was subsequently treated with high-dose steroids, IVIG, as well as rituximab. Following treatment, the patient was successfully extubated and eventually showed complete resolution of the anemia. This case is novel as it represents AIHA likely secondary to EBV viremia in a post-cardiac transplant patient complicated by a severe transfusion reaction. In this circumstance, rituximab in conjunction with standard of care remains an effective treatment of choice.

Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products.

The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. This review summarizes recent advancements in our understanding of the AML TME and its ramifications on current immunotherapeutic strategies. We further review the role of natural products in modulating the TME to enhance response to immunotherapy.

Late renal toxicity in patient with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib: A case report and literature review.

INTRODUCTION: Thyroid carcinoma is the most common endocrine neoplasm. Multimodal therapy including surgery, radioactive iodine (RAI) therapy, and indefinite suppression of thyroid-stimulating hormone has led to an 85% cure rate in differentiated thyroid tumors (DTT). Approximately 5-10% of patients will have recurrence or metastases that have the potential to become resistant to RAI treatment.1 10-year overall survival rates are reported to be 10% in these patients versus 56% in patients with RAI avid disease.2 Lenvatinib, a multi-tyrosine-kinase inhibitor (TKI), was shown to have a 65% overall response rate in addition to a significant improvement in progression-free survival (PFS), approved to treat RAI-resistant DTTs.3, 4. CASE REPORT: We are reporting a very rare case of late renal toxicity in a 68-year-old woman with a history of type 2 diabetes and metastatic RAI-resistant follicular thyroid carcinoma (Hurthle cell variant) who developed thrombotic microangiopathy 21 months after initiation of treatment. MANAGEMENT & OUTCOME: It was determined that LEN should be held, due to worsening renal function secondary to TKI-induced kidney injury. Although the patient's renal function eventually improved and returned to her baseline after discontinuation of LEN, there was marked disease progression after drug cessation. DISCUSSION: Renal toxicity is a rare adverse event (AE) that tends to occur typically within three weeks of initiation of treatment. The utilization of TKIs can lead to glomerulosclerosis, and careful considerations and precautions should be taken by clinicians who intend to initiate TKI therapy in patients with pre-existing diabetes to prevent renal toxicity.

Outcomes of the Pregnancies with Chronic Myeloid Leukemia in the Tyrosine Kinase Inhibitor Era and Literature Review.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) that accounts for 10% of pregnancy-associated leukemias. The Philadelphia chromosome balanced translocation, t (9:22) (q34; q11.2), is the classic mutation seen in CML. The BCR-ABL oncoprotein encoded by this mutation is a constitutively active tyrosine kinase. Tyrosine kinase inhibitor (TKI) therapy is considered a first-line treatment for CML. However, the literature has revealed risks of teratogenicity with TKI therapy during pregnancy. Understanding the risks and benefits of TKI therapy and alternative therapies such as interferon-alpha (IFN-α) will help clinicians and pregnant patients develop a personalized CML treatment plan. This manuscript presents a case series detailing the management of five pregnancies in two pregnant patients with CML and a literature review of CML management in pregnancy.