Testicular Relapse of Primary Diffuse Large B-cell Lymphoma of the Central Nervous System - a Rare Occurrence.

Among diffuse large b-cell lymphoma (DLBCL) subtypes, primary testicular lymphoma (PTL) has one of the highest risks of central nervous system (CNS) relapse. The converse, primary CNS lymphoma (PCNSL) relapse outside the CNS is rare. Molecular analysis has illustrated a genetic similarity between PTL and PCNSL. Here we present a case of a 64-year-old man with testicular relapse of PCNSL 20 months after a complete response to high dose methotrexate-based chemotherapy. His tumor demonstrated a molecular profile similar to both PCNSL and PTL on next generation sequencing, and molecular analysis confirmed common clonal origin of his CNS and testicular lesions. We review prior cases of testicular relapse of PCNSL, which lacked molecular investigations, and discuss the implications of the genomic findings in our patient, including future treatment options.

Objective Impact of Hematology-Oncology Hospitalist Care in an Inpatient Setting.

PURPOSE: The utilization of the hospitalist care model has increased over the past decade because of improved cost-effectiveness, quality of care, and value that it provides. Studies have shown that compared with the traditional care model, use of hospitalists provides cost-saving and improved value to hospital systems. However, the data for the use of oncology hospitalists (ONC Hosp) are sparse. In this study, we investigate the impact of inpatient ONC Hosp on 30-day readmissions, length of stay (LOS), discharge to hospice, and inpatient mortality when compared with a traditional model where outpatient oncologists manage the acute issues of hospitalized patients with cancer. METHODS: Rhode Island Hospital hired ONC Hosps to attend on the inpatient oncology service. To determine the impact of this new patient care model, we performed a retrospective review of oncology patients admitted to Rhode Island Hospital between July 1, 2012, and June 30, 2018, and compared quality outcomes of 30-day readmission, LOS, discharge to hospice, and inpatient mortality to those from the traditional care model. RESULTS: Compared with outpatient oncologists care, care by ONC Hosp was associated with a significant decrease in 30-day readmissions (23.0% v 29.6%, P = .019) and a significant increase in discharge to hospice (18.1% v 12.1%, P < .001). No significant difference was detected between LOS (P = .833) or inpatient mortality (P = .332). CONCLUSION: This study shows that compared with the traditional care model, the use of ONC Hosps has a positive impact on patient care and the potential to add value to the hospital system.

Seroconversion and outcomes after initial and booster COVID-19 vaccination in adults with hematologic malignancies.

BACKGROUND: Patients with hematologic malignancies have impaired humoral immunity secondary to their malignancy and its treatment, placing them at risk of severe coronavirus disease-19 (COVID-19) infection and reduced response to vaccination. METHODS: The authors retrospectively analyzed serologic responses to initial and booster COVID-19 vaccination in 378 patients with hematologic malignancy and subsequently tracked COVID-19-related outcomes. RESULTS: Seroconversion occurred in 181 patients (48%) after initial vaccination; patients who had active malignancy or those who were recently treated with a B-cell-depleting monoclonal antibody had the lowest rates of seroconversion. For initial nonresponders to vaccination, seroconversion after a booster dose occurred in 48 of 85 patients (56%). The seroconversion rate after the booster was similar for patients on (53%) and off (58%) active therapy (p = .82). Thirty-three patients (8.8%) developed a COVID-19 infection, and there were three COVID-19-related deaths (0.8%). Although no significant association was observed between postvaccination seroconversion and the incidence of COVID-19 infection, no patient with seroconversion died from COVID-19, and no patient who received tixagevimab/cilgavimab (N = 25) was diagnosed with a COVID-19 infection. CONCLUSIONS: Booster vaccinations can promote seroconversion in a significant proportion of patients who are seronegative after the initial vaccination course regardless of the specific vaccine or on/off treatment status at the time of revaccination. Although postvaccination seroconversion may not be associated with a decrease in any (including asymptomatic) COVID-19 infection, the authors' experience suggested that effective vaccination (including a booster), supplemented by passive immunization using tixagevimab/cilgavimab in case of lack of seroconversion, effectively eliminated the risk of COVID-19 death in the otherwise high-risk population. LAY SUMMARY: Patients with hematologic malignancy, especially lymphoma, have an impaired response to coronavirus disease 2019 (COVID-19) vaccination. In this single-institution review, less than one half of the patients studied made detectable antibodies. For those who did not make detectable antibodies after initial vaccination, over one half (65%) were able to produce antibodies after booster vaccination. By the end of February 2022, 33 of the original 378 patients had a documented COVID-19 infection. The only deaths from COVID-19 were in those who had undetectable antibodies, and no patient who received prophylactic antibody therapy developed a COVID-19 infection.

Factor XIII Deficiency: A Review of Clinical Presentation and Management.

Factor XIII (FXIII) deficiency is a rare autosomal recessive disorder that can result in life-threatening bleeding and early fetal loss. FXIII not only is responsible for cross-linking fibrinogen to stabilize and strengthen clot formation but also facilitates wound healing and angiogenesis and plays an important role in fetal vitality. Modern therapeutics allow for prophylactic treatment that can prevent most major bleeding and increasing fetal viability. Early diagnosis is paramount due to the high risk of intracranial bleeding.

Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma.

The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)-based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. They included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at a median of 39 months before accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive assay of CSF was associated with a 29% cumulative risk of CNS recurrence within 12 months of diagnosis, in contrast with a 0% risk among patients with negative CSF (P = .045). These observations suggest that detection of clonotypic DNA can aid in the diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay may enhance clinical risk assessment for CNS recurrence among patients with newly diagnosed lymphomas and help select those who may benefit most from novel approaches to CNS-directed prophylaxis.

Tumor lysis syndrome risk in outpatient versus inpatient administration of venetoclax and hypomethlators for acute myeloid leukemia.

INTRODUCTION: Venetoclax along with hypomethylating agents (HMAs) is the new standard therapy for older patients with acute myeloid leukemia (AML) not fit for intensive frontline induction chemotherapy. Venetoclax is associated with fatal episodes of tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL), and recommendations are for its initiation for CLL and AML in the inpatient setting with close monitoring. Herein, we evaluated the safety of outpatient venetoclax ramp up when given in addition to HMAs for the treatment of AML. METHODS: We conducted a retrospective review of patients diagnosed with AML at our institution from 12/1/2016 until 7/1/2020. We identified patients who received HMAs and venetoclax for AML, either as frontline or relapsed/refractory therapy. Records were reviewed for evidence of laboratory or clinical tumor lysis episodes in all patients. RESULTS: Between 12/1/2016 and 7/1/2020 43, patients at our institution received venetoclax/HMA for the treatment of AML. Thirty-nine patients (91%) had venetoclax initiation and ramp up in the outpatient setting. One episode of laboratory TLS (2.5%) was identified. This patient required admission to the hospital for rasburicase and IV fluids with resolution of the laboratory effects without resultant clinical TLS. There were no episodes of clinical TLS in either group. Thirty-day mortality from venetoclax initiation was 0% in both groups. CONCLUSION: Our experience with HMAs and venetoclax showed that outpatient ramp up of venetoclax is safe with a very low risk of laboratory TLS (2.5%) and no evidence of clinical TLS within our cohort.

Adjuvant chemotherapy administration and survival outcomes of lymphoma survivors with common solid tumors: a population-based study†.

Using the Surveillance, Epidemiology, and End Results database (2004-2015), we compared adjuvant chemotherapy use and survival for three common solid tumors in patients with and without history of lymphoma (DLBCL: diffuse large B cell, HL: Hodgkin lymphoma). Among patients with breast (n = 531,243), colon (n = 108,196), and lung (n = 23,179) cancers, we identified 361, 134, and 37 DLBCL survivors, and 349, 73, and 25 HL survivors, respectively. We found no significant difference between lymphoma survivors and controls in the use of adjuvant chemotherapy, except HL survivors with colon cancer, who had a lower rate. Among chemotherapy recipients, OS was significantly worse among HL survivors with all three cancers, and DLBCL survivors with breast cancer (hazard ratio [HR] 1.57-2.28). HL survivors had significantly higher mortality from cardiovascular diseases in breast and lung cancers (sub-HR, 7.96-9.64), which suggests that worse survival in this population might be due to late or cumulative toxicities of cancer-directed treatment.

Acute Myeloid Leukemia: A Review.

Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage (red blood cells, platelets, and white blood cells other than B and T cells). Like other malignancies, it is due to genetic variations that lead to neoplastic changes and clonal proliferation. AML remains a rare malignancy, accounting for only 1.2% of all new cancer diagnoses in the United States per year, but it accounts for close to one third of all leukemias diagnosed.* For much of the 20th and early 21st century treatment paradigms were unchanged with survival curves remaining stagnant for many decades. Recent changes in our understanding of the genetic variations in the disease have led to some promising new therapies with hopes for improved outcomes in the future. Below we review the definitions, diagnosis and classification of AML and how this affects the evolving treatment paradigm of AML.

Refractoriness to red blood cell transfusion therapy due to hypersplenism.

BACKGROUND: A 55-year-old male presented with myelodysplastic/myeloproliferative neoplasm and severe splenomegaly. The patient is blood group O, D+ with a negative indirect antiglobulin test. Transfusion of 5 units of red blood cells (RBCs) increased the hemoglobin (Hb) level from 6.7 to 7.2 g/dL. No active bleeding or hemolysis was evident. The patient was readmitted 1 week later with a Hb level of 3.3 g/dL. An additional 6 units of RBCs showed only an increase from 3.3 to 3.5 g/dL. Partial splenic embolization was performed, which resulted in a stabilization of the Hb level at approximately 7 g/dL. Because of this, total splenectomy was performed, which resulted in a gradual increase in Hb level to approximately 13 g/dL. The patient remains transfusion independent 160 days postsplenectomy. RESULTS: RBC transfusion increases Hb concentration by 1 g/dL per unit in a typical adult. This increase is attenuated in the presence of ongoing hemolysis or active blood loss. Occasionally, a low-RBC-volume unit transfused to a recipient with a large intravascular blood volume may show an unexpectedly small increase. In rare situations, however, the etiology of a greatly attenuated response is more perplexing. The pattern of Hb concentration posttransfusion was suggestive of splenic sequestration in our patient. CONCLUSION: Severe refractoriness to RBC transfusion attributable to severe hypersplenism is a rare event. Our case suggests that splenic artery embolization may be a useful initial approach in individual cases and a potential predictor of the utility of a subsequent surgical splenectomy.

Genetics and diffuse large B-Cell lymphoma.

Diffuse large B-Cell lymphoma (DLBCL) is one of the most common and aggressive subtypes of non-Hodgkin's lymphoma (NHL). Gene expression profiling (GEP) studies have identified at least two distinct molecular subtypes of DLBCL termed as germinal center B-cell (GCB) and activated B-cell (ABC). These molecular subtypes represent lymphomas that are driven by very different intracellular oncogenic signaling pathways which have prognostic value and could potentially be exploited for therapeutic benefit in future. There are other oncogenes, namely BCL-2, BCL-6 and MYC, which have been associated with the pathogenesis of DLBCL. Concurrent presence of two oncogenes is present in about 5% of DLBCL and it is termed "double hit lymphoma" (DHL). DHL are associated with an aggressive clinical course and do not respond well to the standard DLBCL immune-chemotherapy regimen, RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). Other aggressive therapeutic approaches including autologous bone marrow transplant have not shown any survival benefit in this subgroup of DLBCL patients. New strategies in development to address this resistance in DHL include the regimen DA-EPOCH-R (dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab). Recent studies have shown increased sensitivity of DHL to DA-EPOCH-R chemotherapy and will likely be the new standard of care in this subset of DLBCL patients in the future.

Retrograde embolism from the descending thoracic aorta causing stroke: an underappreciated clinical condition.

The mechanism of retrograde aortic blood flow is a complex and underreported clinical phenomenon. Complex plaques of the aortic arch are considered high-risk sources of cerebral emboli.(1) Aortic plaques situated in the descending thoracic aorta are however often overlooked and in fact can be more frequent potential sources of cerebral embolism through the mechanism of retrograde aortic blood flow. We present the case of an elderly Caucasian female who experienced recurrent posterior circulation embolic strokes where the only possible underlying etiology was found to be an atheroma in the descending thoracic aorta, possibly showering retrograde emboli.