Characterized by an aggressive course with a poor overall survival due to treatment refractoriness, plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell B cell lymphoma. Gorham’s ...lymphangiomatosis or Gorham–Stout disease (GSD) is a rare skeletal condition of unknown etiology characterized by progressive bone loss and nonmalignant proliferation of vascular and lymphatic channels within the affected bone. Neither disease has a standard of care. We present a 23-year-old HIV-negative woman with GSD, managed medically with octreotide and sirolimus, who developed PBL. After progressing on V-EPOCH (bortezomib, etoposide, vincristine, cyclophosphamide, doxorubicin, and prednisone), she was treated with daratumumab, lenalidomide, and dexamethasone (DRD) therapy and achieved complete remission after two cycles with progression after eight cycles. This is a report of treatment of PBL with DRD therapy. Clinical investigations of the DRD regimen in PBL in conjunction with other agents to improve both depth and durability of response are warranted.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma. Previous studies have identified MYD88, CD79b and PIM1 as the most common genetic mutations in PCNSL. The ...extent to which mutations vary by ethnicity is unknown. The purpose of this study was to describe differences in genetic mutations and survival by Hispanic ethnicity in PCNSL.
30 patients with PCNSL were examined for mutations in 275 genes by DNA analysis and 1408 genes by RNA analysis utilizing next generation sequencing.
60% of patients were Hispanic. 125 different mutated genes were detected. The most commonly affected genes were: MYD88 (44%), CARD11 (21%), CD79b (17%), PIM1 (17%) and KMT2D (17%) . MYD88 mutation was less frequent in Hispanic patients (27% vs 66%, P=.02). More Hispanic patients had >3 mutated genes (89% vs 55 %. P=.03). Two-year progression-free survival (PFS) and overall survival (OS) in Hispanic vs. non-Hispanic patients (PFS 60% vs 27%, P=.09), (OS 60% vs 36%, P=.23). MYD88, CARD11, PIM1, and KMT2D were not associated with significant differences in OS or PFS. CD79b mutation correlated with superior 2-yr PFS (P=.04).
We identified highly recurrent genetic alterations in PCNSL. Our data suggest that heterogeneity in some mutations may be related to ethnicity. There was no statistically significant difference in 2-yr PFS and OS in our Hispanic patients. Studies on larger population may further help to describe differences in tumor biology, and outcomes in Hispanic patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction:Primary central nervous system lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) with a tropism for the CNS microenvironment. Limited studies suggested differential expression ...of multiple extracellular matrix (ECM) and adhesions-related genes in PCNSL as compared to nodal DLBCL. We used next generation sequencing to evaluate expression profiles of 1408 genes and and performed differential expression profiling to compare PCNSL with nodal DLBCL, CD5+ DLBCL and EBV+ DLBCL. CD5+ DLBCL was selected because it is frequently ABC subtype. We also selected EBV+ DLBCL due to its poor outcome, similar to PCNSL.
Methods:RNA was extracted from 30 formalin-fixed paraffin-embedded (FFPE) tissue samples from PCNSL patients and 23 FFPE tissue samples from cases with lymph node DLBCL-NOS, 8 samples CD5+DLBCL, 14 samples EBV+ DLBCL.. We sequenced the RNA using a 1408 gene panel (Illumina). Next Generation Sequencing was based on hybrid capture methodology. Total number of reads per sample must exceed 5 million to be accepted. RNA levels were quantified using FPKM. Levels of expression of each of the 1408 genes were compared between groups. The T-score is used to show differences. Considering the number of analyzed samples and to correct for multiple testing, only T-score less or greater than 3 was considered clinically significant.
Results:PCNSL showed significant overexpression in 25 genes as compared with CD5+ DLBCL, while only 5 genes were highly expressed in PCNSL as compared with nodal DLBCL and 8 when compared with EBV+ DLBCL (Table below). Four genes were significantly less expressed in PCNSL as compared with CD5+ DLBCL, and only one gene when compared to nodal and EBV+ DLBCL. There was no significant difference in RNA expression of MYD88, CD79B, CARD11, KMT2D or SPP1 between PCNSL and DLBC-NOS, CD5+ DLBCL and EBV+ DLBCL . There was no significant difference between PCNSL and the other sub types in MYC, Ki67, BCL2, CD44, or CD274 (PD-L1) expression. Several genes emerged as highly expressed in PCNSL as compared with other subtypes of DLBCL (negative T-score). However, CLTC (Clathrin Heavy Chain) gene is uniquely highly overexpressed in PCNSL and not in any of the other 3 types of lymphoma. The CLTC gene is involved in anaplastic lymphoma as a partner gene for ALK (CLTC-ALK) in t(2,17) translocation. The SEPT2 (SEPTIN2) gene is uniquely highly expressed in PCNSL as compared with nodal and EBV DLBC lymphoma. SEPT2 gene plays significant role in Hodgkin lymphoma and in maintaining Reed-Stenberg cells . In contrast, VEGFC was significantly lower in PCNSL compared with nodal DLBCL.
Conclusions:RNA molecular profiling suggests significant difference between PCNSL and CD5+ DLBCL and less difference when compared with nodal and EBV+ DLBCL. The strikingly high expression of CLTC gene in PCNSL suggests possible targeting of this gene might present a specific therapeutic approach for PCNSL.
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Abdulhaq:Novartis:Consultancy, Honoraria, Speakers Bureau;Astellas:Honoraria, Speakers Bureau;Amgen:Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Morphosys:Membership on an entity's Board of Directors or advisory committees, Research Funding;Oncopeptide:Research Funding.
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IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Bladder adenocarcinoma is an uncommon type of bladder cancer. Signet ring cell pathology is a rare subtype of bladder adenocarcinoma. Global incidence rates of signet ring cell adenocarcinoma of the ...bladder have not been established. Management of signet cell bladder cancer is challenging as it is aggressive in behavior with frequent relapse despite chemotherapy. Here we present a case of stage IV signet cell bladder cancer with retroperitoneal fibrosis treated with FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) regimen with a complete durable response.
Primary plasma cell leukemia (pPCL) is an uncommon disease. IgM multiple myeloma (MM) is an infrequent subtype that accounts for less than 1 percent of MM cases. IgM pPCL is quite rare with only a ...few cases published to date. We describe a case of a patient with IgM pPCL who initially presented with hyperviscosity syndrome requiring urgent plasma exchange. His bone marrow biopsy demonstrated t(11;14). He progressed on proteasome inhibitors, immunomodulating agents, and other chemotherapy medications but later achieved very good partial response (VGPR) to venetoclax and dexamethasone. Given the poor prognosis of pPCL, further studies using venetoclax alone or in combination with other novel agents as first-line treatment options are warranted particularly in patients with t(11;14).
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Long-term disease-free survival in adults with T-cell acute lymphoblastic leukemia (T-ALL) remains poor, particularly after relapse, with few available salvage options. Preclinical data suggest that ...inhibition of the antiapoptotic protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other agents, may be a unique therapeutic approach for the treatment of T-ALL. We present a case of a young male with T-ALL, relapsed after allogeneic hematopoietic stem cell transplant, who achieved a second complete remission following salvage therapy with combined venetoclax and decitabine. Assessment of measurable residual disease by next generation sequencing showed no evidence of residual disease of a sensitivity of 1 × 10−6. While the combination of venetoclax and hypomethylating agents has shown promise in the treatment of relapsed/refractory AML, and to our knowledge, this is the first report of this combination demonstrating clinical activity in relapsed/refractory T-ALL.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Rosai-Dorfman disease (RDD) is a rare benign histiocytic proliferative disorder predominantly of the lymph nodes, which mostly occurs in children and young adults typically presenting with ...lymphadenopathy. Our case is of a 63 year-old African-American male who presented with subjective fever, weight loss, bilateral axillary and inguinal lymphadenopathy as well as auto-immune hemolytic anemia. The histological analysis showed emperipolesis and histiocytes that were positive for S-100 and CD-68 consistent with RDD. After steroid treatment and splenectomy, patient's symptoms and hemolytic anemia had resolved. Our case is the first case of RDD reported to be associated with auto-immune hemolytic anemia in an adult.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkin Lymphoma (NHL), accounting for approximately 30% of all cases. While NHL mortality rates have shown a ...downward trend over the last two decades, comprehensive investigations into DLBCL mortality trends and disparities across racial, ethnic, gender, and geographical categories in the United States are notably scarce. Methods: Utilizing the Centers for Disease Control and Prevention's (CDC) WONDER database we identified all patients who died from NHL and DLBCL from 2000 to 2020. Age-adjusted mortality rates per 100,000 persons (AAMR) were calculated and standardized to the 2000 US census data. The National Cancer Institute (NCI) Joinpoint Regression Program was used to analyze these data to calculate annual percent changes (APCs) and average annual percent changes (AAPCs). Statistically significant changes were confirmed when the confidence interval for the APC or AAPC did not encompass zero. Additionally, subgroup analyses were conducted based on race, ethnicity, gender, and geographic location. Results: The study identified 434,419 NHL and 46,252 DLBCL deaths. NHL mortality showed a statistically significant average annual decrease of 2.5% (95% CI: -2.7 to -2.4). DLBCL mortality trends varied, initially decreasing from 2000 to 2008, then notably increasing from 2008 to 2011, and subsequently rising moderately from 2011 to 2020. This pattern culminated in a statistically significant overall average annual increase of 3.5% (95% CI: 0.4 to 6.7) in DLBCL mortality. Subgroup analyses revealed that males, Blacks, and Asians or Pacific Islanders experienced the most marked upward trends in DLBCL mortality. Both metropolitan and non-metropolitan areas reported an increase in DLBCL mortality, with metropolitan areas showing a more pronounced rise. Conclusion: Representing the most comprehensive analysis of DLBCL mortality trends to date, our study revealed intriguing disparities among the subgroups we investigated, along with an upward trend in mortality rates that departs from previously reported data. The divergence could be attributed, in part, to the expansive population coverage of the database we utilized and the use of death certificates, which may present discrepant results from other cancer registries. These findings underscore the necessity for ongoing research, guiding the development of targeted intervention strategies for DLBCL and informing efforts to bridge the identified disparities.
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IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
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