Complete response in a frail patient with high-grade B-cell lymphoma to only one cycle of R-CHOP or to prolonged COVID-19?

Abstract Introduction High-grade B-cell lymphomas are a subgroup of lymphomas characterized by high-grade morphological appearances and the presence of rearrangements in MYC in addition to BCL2 and/or BCL6 (HGBL-DH/TH) or in the absence of cytogenetic changes, HGBL-NOS, previously described as B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma (BCLU). These entities have been shown to have poorer outcomes from conventional treatment compared with diffuse large B cell lymphomas (DLBCL) not otherwise specified. One feature contributing to the poor prognosis of DHL is increased risk of central nervous system (CNS) involvement. Intensive chemotherapy regimens which include CNS prophylaxis may improve PFS in HGBL compared with R-CHOP-like therapy. Methods We conducted an international, multi-center retrospective analysis of HGBL-DH/TH/NOS and BCLU. The association between baseline clinical and histopathological characteristics and clinical outcome was assessed by Cox proportional hazards model, and variables with P<0.10 by univariate analysis were included in multivariate Cox regression. Results 57 patients were included - 20 patients with MYC/BCL2 rearrangements, 6 patients with MYC/BCL6 rearrangements, 13 with MYC/BCL2/BCL6 rearrangements, 16 with the WHO 2008 BCLU classification and 2 with HGBL-NOS classification. 16 (28%) patients had evidence of transformation from antecedent or synchronously diagnosed indolent lymphoma. The median age at diagnosis was 63 years (range 39-86), with 30 (53%) male and median year of diagnosis was 2015 (range 2011 - 2017). The majority of patients were Stage III/IV [n=42, 74%] and ECOG ≤ 1 [n=44, 77%]. 40 patients (70%) had raised LDH at diagnosis; in 15 (26%) LDH was ≥3x ULN. Bone marrow involvement with high-grade lymphoma and extranodal involvement (excluding bone marrow) were present in 9 (16%) and 34 (60%) patients respectively. The median number of extranodal sites of involvement was 1 (range 0-10). Of 32 patients (56%) who underwent CNS staging at diagnosis, 2 (6%) had CNS involvement at baseline- one diagnosed with CSF cytology, and the other by combined modalities (CSF flow cytometry, cytology and MRI). R-CHOP was the most common initial (49%) and ongoing (39%) induction chemotherapy regimen, followed by dose-adjusted EPOCH (32%), R-HyperCVAD and R-CODOX-M/IVAC (7% each) and other regimens (9%). A predominance of patients [n=33, 58%] received a form of CNS directed treatment- 8 (14%) as a standard component of the chosen induction regimen, and 25 (44%) as an addition to induction treatment (intrathecal [n=18, 32%], systemic therapy [n=2, 4%] or both [n=5, 9%]). At a median follow-up of 25 months (range 5-67), the 2 year PFS and OS was 68% (95% CI: 50-81%) and 74% (95% CI: 55-85%) respectively for HGBL-DH/TH and 67% (95% CI: 40-83%) and 72% (95% CI: 46-87%) for BCLU/HGBL-NOS (Figure 1). Outcomes between the R-CHOP and intensive chemotherapy regimens were similar. At 2 years PFS was 70% (95% CI: 44-86%) vs 73% (95% CI: 52-86%), and OS was 79% (95% CI: 52-92%) vs 76% (95% CI: 56-89%). Two patients experienced CNS progression- one in a patient with BCLU and documented CNS disease at diagnosis, and another as a presentation of CNS relapse in a patient with HGBL-TH without evidence of CNS disease at diagnosis who did not receive specific CNS prophylaxis. Raised LDH was adversely prognostic for PFS in entire cohort and ECOG >2 was adversely prognostic for OS in the BCLU/HGBL-NOS group. Among patients who achieved a complete response at end of treatment, the 2 year PFS and OS was 96% (95% CI: 75-99%). In patients who had non-complete response (PD, SD, PR) the 2 year PFS and OS was 29% (95% CI: 13-48%) and 42% (95% CI: 22-62%) respectively. Among 23 patients (40%) with Deauville scores reported, those with Deauville score of 1-3 had a 2 year PFS and OS of 100%, with no events amongst 17 patients. Conclusion Within the limits of a retrospective analysis, outcomes of HGBL-DH/TH and HGBL-NOS/BCLU were similar. Rates of CNS involvement at diagnosis and on relapse were comparable with other retrospective series. Negative end of treatment PET-CT (DS 1-3) identifies a subset of patients with favorable prognosis. Disclosures Jeyasekharan: AstraZeneca: Other: Collaboration; Merck Sharp & Dohme: Honoraria; Janssen: Research Funding; PerkinElmer: Other: Collaboration. Bishton:Gilead: Research Funding; Abbvie: Research Funding; Roche: Research Funding; Takeda: Other: travel support to ASH.

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Outcomes of High Grade B- Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements: An Atlantic Canadian Centre Perspective

Blood ◽

10.1182/blood-2021-153585 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4579-4579

Author(s):

Erica Kelly ◽

Nicholas Allen Forward ◽

Mary-Margaret Keating

Keyword(s):

Overall Survival ◽

B Cell ◽

Burkitt Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Small Sample ◽

Optimal Treatment ◽

Clinical Entity ◽

High Grade

Abstract Background: High Grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (also known as Double-hit lymphoma (DHL)) is an aggressive B cell Non-Hodgkin lymphoma which has recently been recognized by the WHO as a distinct clinical entity from Diffuse Large B cell lymphoma (DLBCL). Compared to patients with DLBCL, patients with DHL have poor outcomes with standard R-CHOP chemoimmunotherapy, and the optimal treatment regimen for this high-risk lymphoma is unknown. Due to clinical and genetic overlap with Burkitt lymphoma (which shares translocations involving MYC), treatment of DHL with more intensive Burkitt lymphoma protocols is a common approach. However, these regimens are associated with significant toxicity, and the superiority of these regimens over standard R-CHOP remains uncertain. At our institution, R-CODOX-M/IVAC has been the preferred regimen for fit younger patients with DHL. Objective: To review the outcomes of patients with DHL treated with R-CODOX-M/IVAC at our institution. Methods: In this retrospective single-centre study, patients with DHL receiving R-CODOX-M/IVAC were identified by cross-referencing provincial cancer care data and hospital pharmacy data. All adult patients with a diagnosis of DHL and who were treated with R-CODOX-M/IVAC between January 2009 and January 2019 were included in the analysis. The primary outcomes is complete response (CR) per standard lymphoma response criteria. Secondary outcomes include median progression-free survival (PFS), overall survival at 1 year, and median overall survival. Kaplan-Meier analysis was used for survival analyses. Results: 14 patients with DHL and meeting the inclusion criteria were identified and included in the analysis. The complete response rate was 35.7%. With a median followup time of 26 months, the median PFS was 31.8 months, and the median OS was 54.3 months. The overall survival at 1 year was 77%. Conclusions: A previous meta-analysis demonstrated inferior outcomes for patients with DHL receiving RCHOP, with a median PFS of only 12.1 months. The optimal treatment of these patients remains to be defined. Dose-adjusted regimens have been associated with a significant improvement in PFS compared to RCHOP (21.6 months versus 12.1 months). Previous retrospective data suggests R-CODOX-M/IVAC results in more favourable outcomes 2 year PFS of 41% and 2 year OS of 53% (Sun et al., Clinical Lymphoma, Myeloma & Leukemia, 2015). Our data, although limited, that R-CODOX-M/IVAC may be associated with improved outcomes compared to published results with RCHOP. The limitations of this study include its retrospective design, lack of matched controls receiving RCHOP, and its small sample size. Nevertheless, this study adds to the small body of available evidence on this difficult to treat clinical entity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL

Acta Haematologica Polonica ◽

10.2478/ahp-2019-0018 ◽

2019 ◽

Vol 50 (3) ◽

pp. 109-115

Author(s):

Beata Grygalewicz

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

World Health ◽

High Grade ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Health Organization ◽

Large B Cell

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.

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Prognostication of High-Grade Diffuse Large B-Cell Lymphoma and the Role of MYC, BCL2, and Phosphohistone H3

American Journal of Clinical Pathology ◽

10.1093/ajcp/144.suppl2.145 ◽

2015 ◽

Vol 144 (suppl 2) ◽

pp. A145-A145

Author(s):

Qian Dai ◽

Shuko Harada ◽

Deniz Peker

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Grade ◽

Large B Cell Lymphoma ◽

Phosphohistone H3 ◽

Large B Cell

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A Challenging Case of A Myeloid Sarcoma Misdiagnosed as High Grade B-Cell Lymphoma

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.212 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S97-S97

Author(s):

A Herrmann ◽

B Mai ◽

S Elzamly ◽

A Wahed ◽

A Nguyen ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Myeloid Sarcoma ◽

Proliferation Index ◽

High Grade ◽

Cell Markers ◽

Thoracolumbar Region ◽

The Right

Abstract Introduction/Objective A 46-year-old female presented with severe back pain associated with progressive bilateral lower extremity weakness and paresthesia, urinary retention, and constipation. Computed tomography revealed a retroperitoneal mass encasing the right psoas muscle, obstructing the right kidney, and extending to the thoracolumbar region resulting in severe spinal compression. An epidural tumor resection was subsequently performed at an outside hospital. Methods Histological sections showed sheets of blastoid neoplastic cells with intermediate to large nuclei, irregular membranes, fine chromatin, and prominent nucleoli. Immunohistochemical stains showed that these cells were positive for CD43, CD79a (weak, focal), BCL2, C-MYC, and PAX5 (weak, focal) and negative for CD10, CD20, CD30, ALK1, BCL6, MUM1, and Tdt. The Ki-67 proliferation index was 75-80%. With this immunophenotype, this patient was diagnosed with a high grade B-cell lymphoma and transferred to our institution for further work-up. On review of the slides, further immunohistochemical testing was requested which revealed positivity for CD117 and myeloperoxidase (MPO). Results The overall morphological and immunophenotypical features are most compatible with myeloid sarcoma (MS) with aberrant expression of B-cell markers and this patient’s diagnosis was amended. Interestingly, the patient’s bone marrow examination only showed 2% myeloblasts with left shifted granulocytosis and concurrent fluorescence in situ hybridization (FISH) studies were negative. Conclusion A literature review showed that 40-50% of MS are misdiagnosed as lymphoma. MS can frequently stain with B-cell or T-cell markers, as seen in this case, which makes it challenging for an accurate diagnosis and sub- classification. In addition, our case is interesting in that there was only extramedullary presentation without bone marrow involvement. Typically, MS develops after the diagnosis of acute myeloid leukemia (AML) with an incidence of 3–5% after AML. It can also manifest de novo in healthy patients, who then go on to develop AML months to years later. Therefore, this patient will require close follow-up.

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