A Case Series on the Use of Brentuximab Vedotin for the Treatment of Mycosis Fungoides.

BACKGROUND: Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to current standard-of-care treatments.   Objective: To determine the real-world efficacy and adverse effects of BV use in patients with mycosis fungoides (MF) who were treated with BV at Atrium Health Wake Forest Baptist Medical Center. METHODS: Study staff performed a retrospective chart review of patients diagnosed with MF who were prescribed BV at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. RESULTS:   Regardless of their response to BV, all patients in our cohort had higher CD30 positivity on subsequent biopsies compared to their initial skin biopsy.  Conclusions: Improved understanding of appropriate CD30 testing and evaluation will allow for quicker invention of patients with BV responsive CTCL.  J Drugs Dermatol. 2023;22(12):e33-e34.    doi:10.36849/JDD.6981e.

Response and local control in patients treated with low-dose radiotherapy for tumoral mycosis fungoides.

Low-dose radiotherapy (LDRT), defined in this study as 2 fractions of 4 Gy delivered on consecutive days, is an effective option for local palliation of mycosis fungoides (MF), but its efficacy for tumoral lesions (TL) needs investigation. We assessed response and local control (LC) rates for patients treated with LDRT for MF and compared these outcomes between TL and non-TL. A total of 73 lesions in 18 patients treated with LDRT between 2013-2020 were analyzed. Response was defined as complete response (CR), partial response (PR), or no response (NR). In the non-TL versus TL groups, CR was observed in 16.7% v. 4.0%, PR in 81.2% v. 80.0%, NR in 2.1% v. 16.0%, respectively. 2-year LC was 100% for non-TL and 61% for TLs (p < 0.01). LDRT yields excellent response and lesion control for non-TLs and is associated with lower response rates and LC for TLs.

Low-dose radiation therapy yields excellent response and lesion control for non-tumoral lesions.

Clinical Reasoning: A 65-Year-Old Woman With Cancer History and Wrist Drop.

Wrist drop is a common presentation in neurology. To localize the lesion, clinicians can focus on testing finger extension, elbow flexion with semipronated forearm, and elbow extension among other muscle groups and identifying dermatomes of numbness. Once the lesion is localized, electrophysiology or imaging can guide to an underlying etiology. Here, we describe a case that illustrates the importance of using a stepwise approach to diagnose the etiology of wrist drop in a patient with a cancer history. A 65-year-old woman with diffuse large B-cell lymphoma in remission presented with new onset wrist drop, severe pain, numbness, and tingling concerning for peripheral nerve injury. Imaging findings from PET, venous ultrasound, nerve conduction velocity study, and MRI were conflicting favoring deep venous thrombosis, cancer recurrence, or peripheral nerve sheath tumor. A biopsy was ultimately required to confirm the diagnosis.

Identification of high-risk monomorphic post-transplant lymphoproliferative disorder following solid organ transplantation.

Monomorphic post-transplant lymphoproliferative disorder (M-PTLD) occurring after solid organ transplant histologically resembles aggressive non-Hodgkin lymphomas, with diffuse large B-cell lymphoma being the most common. In a cohort of 40 patients with DLBCL-type M-PTLD, inferior progression free survival (PFS) was observed for Revised International Prognostic Index (R-IPI) >2 (p = 0.01) and high-risk pathologic features (p = 0.02), defined by double expressor lymphoma, MYC rearrangement, or increased copy number of either MYC or BCL2. Overall survival (OS) was inferior in R-IPI >2 (p = 0.002) and high-risk pathologic features (p = 0.003). Combining both R-IPI >2 and high-risk pathologic features resulted in well-delineated good, intermediate, and poor risk groups of DLBCL-type M-PTLD with respect to both PFS and OS (p < 0.001). Our results demonstrate a prognostic role for both the R-IPI score and presence of high-risk pathologic features in DLBCL-type M-PTLD.

Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements.

High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60% had high-grade cytological features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95% confidence interval) 5-year overall survival was 49% (37%-64%). Transformation from previously treated and untreated low-grade lymphoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R-CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not associated with inferior overall survival.

Hyperglycemia during first-line R-CHOP or dose adjusted R-EPOCH chemotherapy for non-Hodgkin lymphoma is prevalent and associated with chemotherapy alteration - a retrospective study.

High-dose glucocorticoids such as prednisone are combined with cytotoxic chemotherapy in the R-CHOP or dose adjusted R-EPOCH regimens used for non-Hodgkin lymphoma (NHL). In this retrospective study, our primary objective was to evaluate the incidence of hyperglycemia during first-line R-CHOP or DA-EPOCH-R. The secondary objectives were to evaluate the incidence of chemotherapy alteration and overall survival in those with and without hyperglycemia. One hundred and sixty patients were eligible. We found that 47% of all patients had at least one hyperglycemic episode and hyperglycemia was associated with chemotherapy alteration (p = .028). Multivariate analysis revealed international prognostic index (IPI) ≥ 3 (p = .045) and chemotherapy alteration (p = .001) were associated with decreased overall survival. We conclude that hyperglycemia is common during first-line NHL treatment with R-CHOP or DA-EPOCH-R, even in the absence of known diabetes and is associated with alterations of chemotherapy. Baseline pre-PET scan fasting blood glucose of 100 mg/dL or higher may predict hyperglycemia during therapy.

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma.

INTRODUCTION: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and compensate for increased drug clearance. The goal of the present study was to examine the risk factors and outcomes of patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. PATIENTS AND METHODS: We report the data from 136 patients with previously untreated aNHL who received infusional DA-EPOCH chemotherapy with or without rituximab from 2005 to 2013. Overall survival was estimated using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine the factors associated with death, progression, or relapse at 2 years. RESULTS: The overall response rate was 82%. The relapse-free survival rate at 1, 3, and 5 years was 68%, 63%, and 52% with 95% confidence intervals (CIs) of 0.59% to 0.85%, 0.54% to 0.70%, and 0.31% to 0.70%, respectively. Patients with T-cell aNHL had an increased risk of death, progression, or relapse (Odds Ratio, 3.5; 95% CI, 1.4-8.8) compared with those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow, and the number of cycles completed were independent predictors of death and relapse. CONCLUSION: Our data suggest that EPOCH with or without rituximab is active in both B- and T-cell aNHL. Toxicity did not significantly affect timing of treatment delivery or treatment outcomes. Dose adjustment by hematopoietic nadir similarly had no effect. The effect of smoking during chemotherapy should be evaluated further.

Acquired Von Willebrand syndrome secondary to mitral and aortic regurgitation.

The association between aortic stenosis and gastrointenstinal bleeding due to acquired von Willebrand syndrome (AVWS) has been well established. We report a patient with AVWS from underlying severe endocarditis-associated aortic regurgitation and pre-existing mitral regurgitation. Cardiovascular disease-related AVWS occurs from a selective loss of the largest multimers of von Willebrand factor from high shear forces, and desmopressin leads to transient clinical improvement.

An unusual presentation of heparin-induced thrombocytopenia in the setting of catheter-directed ablation of atrial fibrillation.

Heparin-induced thrombocytopenia type 2 is an immune-mediated phenomenon associated with heparin exposure that has the potential to evolve into life-threatening thrombosis if not recognized and treated early. Lack of immediate availability of a confirmatory assay often leaves the diagnosis to the clinician's discretion. Despite a high negative predictive value, the clinical '4Ts' scoring system carries a small but a real risk of missing the diagnosis, especially with atypical presentations. We describe one such case of rapid-onset, heparin-induced thrombocytopenia with thrombosis that developed in the setting of catheter-directed ablation of atrial fibrillation, several months after a brief exposure to low-molecular-weight heparin. The clinical scenario as well as the risk of progressing to catastrophic complications prompted immediate discontinuation of all heparin products and treatment with a direct thrombin inhibitor, despite a low pretest clinical score.

Urinoma presenting as an abscess in an immunocompromised host: a case report.

INTRODUCTION: This case report illustrates the relatively rare occurrence of a urinoma masquerading as an abscess in a patient with refractory recurrent non-Hodgkin's lymphoma. Although urinomas have been reported after urinary instrumentation, our case was confounded by a concurrent pleural effusion, an immunocompromised host, and clinical appearance and subsequent incision and drainage that was consistent with an abscess. Although not the first case reported in the literature, the constellation of findings in our patient demonstrates the importance of including urinoma in the differential diagnosis of patients with flank mass. CASE PRESENTATION: Here we report a case of a retroperitoneal fluid collection found in an immunocompromised 65-year-old Caucasian woman. She had recurrent non-Hodgkin's lymphoma and was neutropenic when the collection was found. Drainage of the fluid demonstrated infection, but the case was complicated by increasing fluid production and the development of an ipsilateral pleural effusion. Despite pleural drainage, the abscess output continued to be high. A computed tomography scan demonstrated fluid collection around the renal calices suggestive of rupture; analysis of the fluid was suggestive of a urinoma. The etiology, pathogenesis, and treatment of urinomas in such patients are discussed. CONCLUSIONS: Urinomas can present in patients who have had urinary tract instrumentation or trauma, but can occur in other hosts. Patients with hematologic malignancy can develop malignant or sympathetic pleural effusions and are at risk for skin and soft tissue infections. Clinicians caring for immunocompromised patients, particularly hematologists, oncologists, and transplant clinicians, should be aware of this potential complication because rapid identification and attempt at correction are important to optimize outcome.

Plasma cytokines in polycythemia vera: phenotypic correlates, prognostic relevance, and comparison with myelofibrosis.

Plasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates with disease phenotype and prognosis. In this study, we show that several plasma cytokines are also abnormally expressed in polycythemia vera (PV; n = 65), compared to normal controls (n = 35), but with a significantly different pattern than that of PMF (n = 127). Direct phenotypic correlation in PV included levels of IL-12 with hematocrit; IL-1b, IL-2, IL-7, FGF-b, and HGF with leukocytosis; and IFN-α and IFN-γ with thrombocytosis. In univariate analysis, levels of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP-1ß remained significant on multivariable analysis that included the other cytokines as covariates. Increased level of MIP-1ß (P < 0.01), older age (P < 0.01), and leukocytosis (P = 0.03) maintained their association with shortened survival, on multivariable analysis. This study provides preliminary observations that warrant a larger scale study and suggests the value of plasma cytokines as prognostic biomarkers in PV.

One thousand patients with primary myelofibrosis: the mayo clinic experience.

OBJECTIVE: To share our decades of experience with primary myelofibrosis and underscore the importance of outcomes research studies in designing clinical trials and interpreting their results. PATIENTS AND METHODS: One thousand consecutive patients with primary myelofibrosis seen at Mayo Clinic between November 4, 1977, and September 1, 2011, were considered. The International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS), and DIPSS-plus were applied for risk stratification. Separate analyses were included for patients seen at time of referral (N=1000), at initial diagnosis (N=340), and within or after 1 year of diagnosis (N=660). RESULTS: To date, 592 deaths and 68 leukemic transformations have been documented. Parameters at initial diagnosis vs time of referral included median age (66 vs 65 years), male sex (61% vs 62%), red cell transfusion need (24% vs 38%), hemoglobin level less than 10 g/dL (38% vs 54%), platelet count less than 100 × 10(9)/L (18% vs 26%), leukocyte count more than 25 × 10(9)/L (13% vs 16%), marked splenomegaly (21% vs 31%), constitutional symptoms (29% vs 34%), and abnormal karyotype (31% vs 41%). Mutational frequencies were 61% for JAK2V617F, 8% for MPLW515, and 4% for IDH1/2. DIPSS-plus risk distributions at time of referral were 10% low, 15% intermediate-1, 37% intermediate-2, and 37% high. The corresponding median survivals were 17.5, 7.8, 3.6, and 1.8 years vs 20.0, 14.3, 5.3, and 1.7 years for patients younger than 60 years of age. Compared with both DIPSS and IPSS, DIPSS-plus showed better discrimination among risk groups. Five-year leukemic transformation rates were 6% and 21% in low- and high-risk patients, respectively. CONCLUSION: The current document should serve as a valuable resource for patients and physicians and provides context for the design and interpretation of clinical trials.

Epstein-Barr virus-associated nephrotic syndrome.

Acute infection with Epstein-Barr virus (EBV) causes fever, fatigue and pharyngitis. Renal involvement in systemic EBV infections typically manifests as acute tubular necrosis or tubulointerstitial nephritis. Rarely, EBV infection causes nephrotic syndrome due to minimal change disease. A 22-year-old male with infectious mononucleosis (IM) presented with nephrotic syndrome. Renal biopsy showed minimal change disease with diffuse foot process effacement of the podocytes. Treatment with methylprednisone led to rapid and complete clinical remission. Minimal change nephropathy is a very rare manifestation of EBV infection and should be considered in patients with IM and proteinuria.

Benzodiazepine use in breast cancer survivors: findings from a consecutive series of 1,000 patients.

OBJECTIVE: This study reports the percentage of breast cancer survivors receiving ongoing benzodiazepines and the circumstances surrounding their usage. METHODS: The medical records of 1,000 consecutive breast cancer survivors who were no longer receiving adjuvant chemotherapy were reviewed. RESULTS: Among those patients, 7.9% (95% confidence interval 6.2-9.6; higher than the 3% rate in the general population) were receiving benzodiazepines. Lorazepam was most commonly prescribed. Sixty-eight patients were cancer free at their last visit, and 51 had not been taking benzodiazepines prior to their cancer diagnosis. Anxiety was the single most frequent reason for initiating and continuing benzodiazepines. CONCLUSION: Anxiety appears to be a common explanation for relatively high rates of benzodiazepine use in breast cancer survivors. This finding merits further study.

Predictors of greater than 80% 2-year mortality in primary myelofibrosis: a Mayo Clinic study of 884 karyotypically annotated patients.

DIPSS-plus (the Dynamic International Prognostic Scoring System-plus) includes 8 risk factors for survival in primary myelofibrosis. In the present study of 884 karyotypically annotated patients with primary myelofibrosis, we sought to identify 1 or 2 parameters that can reliably predict death in the first 2 years of disease. After a median of 8.2 years from time of referral to the Mayo Clinic, 564 deaths (64% of patients in the study) had been recorded. Risk factors associated with > 80% 2-year mortality included monosomal karyotype, inv(3)/i(17q) abnormalities, or any 2 of the following: circulating blasts > 9%, leukocytes ≥ 40 × 10(9)/L, or other unfavorable karyotype. Patients with any 1 of these risk profiles (n = 52) displayed significantly shorter overall survival than those otherwise belonging to a high-risk category per DIPSS-plus (n = 298); respective median survivals were 9 and 23 months (hazard ratio 2.2, 95% confidence interval 1.6-3.1; P < .01). The present information complements DIPSS-plus in the selection of primary myelofibrosis patients for high-risk treatment approaches.

Monosomal karyotype in primary myelofibrosis is detrimental to both overall and leukemia-free survival.

Survival in cytogenetically high-risk patients with acute myeloid leukemia or myelodysplastic syndromes is significantly worse in the presence of a monosomal karyotype (MK). The objective of the present study was to determine whether the same held true for primary myelofibrosis. Among 793 primary myelofibrosis patients seen at our institution, 62 displayed an unfavorable karyotype by way of complex karyotype (n = 41) or sole trisomy 8 (n = 21). Seventeen (41%) of the 41 patients with complex karyotype were classified as having an MK. Median survival was 6, 24, and 20 months in patients with MK, complex karyotype without monosomies, and sole trisomy 8, respectively (P < .0001). The corresponding 2-year leukemic transformation rates were 29.4%, 8.3%, and 0 (P < .0001); hazard ratios (95% confidence intervals) were 6.9 (1.3-37.3) and 14.8 (1.7-130.8). The prognostic relevance of MK was not accounted for by the Dynamic International Prognostic Scoring System. We conclude that MK in primary myelofibrosis is associated with extremely poor overall and leukemia-free survival.

Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study.

PURPOSE: Abnormal cytokine expression accompanies myelofibrosis and might be a therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance. PATIENTS AND METHODS: Patients included in this study were required to have archived plasma, bone marrow biopsy, and cytogenetic information available at the time of first referral to the Mayo Clinic. Multiplex biometric sandwich immunoassay was used to measure plasma levels of 30 cytokines. RESULTS: In total, 127 PMF patients were studied; comparison with normal controls (n = 35) revealed significantly increased interleukin-1ß (IL-1ß), IL-1RA, IL-2R, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, tumor necrosis factor α (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon alfa (IFN-α), macrophage inflammatory protein 1α (MIP-1α), MIP-1ß, hepatocyte growth factor (HGF), IFN-γ-inducible protein 10 (IP-10), monokine induced by IFN-γ (MIG), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) levels and decreased IFN-γ levels. In treatment-naive patients (n = 90), increased levels of IL-8 (P < .001), IL-2R (P < .001), IL-12 (P < .001), IL-15 (P = .001), and IP-10 (P = .003) were independently predictive of inferior survival. A similar multivariable analysis that included all 127 study patients confirmed the prognostic value of these five cytokines, and IL-8, IL-2R, IL-12, and IL-15 remained significant when risk stratification, according to the recently revised Dynamic International Prognostic Scoring System (DIPSS plus), was added to the multivariable model. Leukemia-free survival was predicted by IL-8, which was also the only cytokine associated with ≥ 1% circulating blasts. Other cytokine-phenotype associations included increased IL-8 and constitutional symptoms; IL-2R, IL-12, and transfusion need; IL-2R, IL-8, and leukocytosis; IP-10 and thrombocytopenia; HGF, MIG, IL-1RA, and marked splenomegaly; and IL-1RA, IL-2R, IP-10, MIP-1ß, and JAK2V617F. A two-cytokine (IL-8/IL-2R) -based risk categorization delineated prognostically different groups within specific DIPSS plus risk categories. CONCLUSION: This study signifies the presence of specific cytokine-phenotype associations in PMF and a prognostically relevant plasma cytokine signature that might prove useful as a laboratory tool for predicting and monitoring treatment response.