Reply to A. Korfel et al

Schmitz, Norbert; Nickelsen, Maike

doi:10.1200/jco.2016.66.4730

Cited by 8 publications

(10 citation statements)

References 3 publications

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“…Break-apart FISH testing (Vysis LSI, Abbott) was performed on biopsies with DLBCL morphology from population-based registry cohorts from the British Columbia Cancer Agency 9 (tissue microarrays [TMAs] and whole sections), the Conventional Chemo Vs HD Chemo Followed by Auto SCT in Younger Pts With Aggressive Non-Hodgkin's Lymphoma trial (MegaCHOEP; TMAs) 10 , Rituximab with CHOP Over Age 60 Years trial (RICOVER60; TMAs ) [11][12][13][14] [MegaCHOEP and RICOVER60], and R.L.K., W.R.M. [E1412]) using thresholds of $40% and $50% to define positivity, respectively.…”

Section: Methodsmentioning

confidence: 99%

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

Scott

King

Staiger

et al. 2018

Blood

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182

173

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High-grade B-cell lymphoma with and and/or rearrangements (HGBL-DH/TH) is a newly defined entity in the latest World Health Organization Classification. Accurate diagnosis would appear to mandate fluorescence in situ hybridization (FISH) for all tumors with diffuse large B-cell lymphoma (DLBCL) morphology. We present the results of FISH, cell-of-origin, and immunohistochemistry (IHC) testing from 1228 DLBCL biopsies from 3 clinical trials and a population-based registry. HGBL-DH/TH made up 7.9% of the DLBCL, confined primarily to the germinal center B-cell-like (GCB; 13.3%) compared with activated B-cell-like (ABC; 1.7%) subtype ( < .001). HGBL-DH/TH with rearrangement is a GCB phenomenon with no cases observed in 415 ABC DLBCL. A screening strategy restricting FISH testing to tumors of GCB subtype (by Lymph2Cx or Hans IHC) plus dual protein expression of MYC and BCL2 by IHC could limit testing to 11% to 14% of tumors, with a positive predictive value of 30% to 37%; however, this strategy would miss approximately one-quarter of tumors with HBGL-DH/TH with rearrangement and one-third of all HGBL-DH/TH. These results provide accurate estimation of the proportion of HGBL-DH/TH among tumors with DLBCL morphology and allow determination of the impact of various methods available to screen DLBCL tumors for FISH testing.

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Section: Methodsmentioning

confidence: 99%

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

Scott

King

Staiger

et al. 2018

Blood

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182

173

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“…35 Further intensification strategies including autologous stem cell transplant for patients in first remission have resulted in conflicting results, and some trials have revealed a benefit to this approach while others have not. 36,37 A meta-analysis of patients undergoing an autologous stem cell transplant during first remission did not confirm an advantage to a more intensive approach. 36 A US intergroup trial, which limited autologous stem cell transplant to patients with an age-adjusted high-intermediate or high-risk IPI score, did suggest benefit with autologous transplant during first remission.…”

Section: Diffuse Large B-cell Lymphomamentioning

confidence: 97%

Non-Hodgkin Lymphoma: Diagnosis and Treatment

Ansell

2015

Mayo Clinic Proceedings

148

130

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Non-Hodgkin lymphomas are lymphoid malignant neoplasms with diverse biological and clinical behavior. Patients typically present with persistent painless lymphadenopathy, but some patients may present with constitutional symptoms or with involvement of organs other than the lymphoid and hematopoietic system. An accurate diagnosis, careful staging of the disease, and identification of adverse prognostic factors form the basis of treatment selection. Patients commonly receive chemoimmunotherapy as initial treatment, and radiation therapy may be added if patients have early-stage disease. Most patients respond well to treatment, but relapses are frequent and additional therapies including stem cell transplant are often needed. Because many subtypes of lymphoma remain incurable with current management strategies, clinical trials are in progress to identify novel therapies with promising activity in this disease.

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“…Overall, the LBC-05 regimen seemed to be better tolerated than other intensive treatment approaches. 5,10,11 It is thus possible that the favorable outcome is partially related to lower toxicity, which does not interfere with the therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 R-MegaCHOEP, in turn, is not superior to R-CHOEP-14 and is associated with significantly more toxicity. 10 Likewise, rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HCVAD)/rituximab, high-dose methotrexate (HD-Mtx), and cytarabine (R-MA) did not differ from R-CHOP with respect to survival due to high treatment-related mortality. 11 In addition to a high risk of systemic relapse, patients with DLBCL are at risk for progression of their lymphoma in the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis

et al. 2020

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Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates. This trial was registered at www.clinicaltrials.gov as #NCT01325194.

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Reply to A. Korfel et al

Cited by 8 publications

References 3 publications

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

Non-Hodgkin Lymphoma: Diagnosis and Treatment

Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis

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