Prognostic impact of history of follicular lymphoma, induction regimen and stem cell transplant in patients withMYC/BCL2double hit lymphoma

Abstract

MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma. Patients received induction chemotherapy regimens including 61 R-CHOP, 31 R-EPOCH, 29 R-Hyper-CVAD, and 23 other regimens. Thirty-nine patients received a stem cell transplant (SCT) including 31 autologous and 8 allogeneic. Sixty-two patients achieved complete remission (CR) after induction chemotherapy. Median overall survival (OS) was 19 months. Clinicopathologic features were similar between patients with de novo tumors versus those with a history of FL (P > 0.05). Using multivariate analysis, achieving CR, undergoing SCT, stage and the International Prognostic Index were independent prognostic factors for OS. Stem cell transplantion was associated with improved OS in patients who failed to achieve CR, but not in patients who achieved CR after induction chemotherapy. In conclusion, patients with MYC/BCL2 DHL who present with de novo disease and patients with a history of FL have a similarly poor prognosis. Achievement of CR, regardless of the induction chemotherapy regimen used, is the most important independent prognostic factor. Patients who do not achieve CR after induction chemotherapy may benefit from SCT.

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas

“…All the cases were diagnosed as either diffuse large Bcell lymphoma or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma based on their morphological features and all cases were classified as high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements based on the current WHO classification. The study group was further compared to 157 cases of MYC/BCL2 double hit lymphoma and 13 cases of MYC/BCL6 double hit lymphoma that have been reported previously [18,19,21] ( Table S1). The overall survival (overall survival) of patients with triple hit lymphoma was also further compared with a group (n = 467) of patients with diffuse large B-cell lymphoma without MYC rearrangement.…”

“…Multiple retrospective studies have shown that patients with double hit lymphoma usually have an aggressive clinical course and very poor outcome [15][16][17][18][19][20][21][22][23][24]. Extranodal disease, a high serum lactate dehydrogenase level, bone marrow and central nervous system involvement and a higher international prognostic index score are frequent in double hit lymphoma patients.…”

P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma

“…Positivity for MYC, BCL2, and P53 expression was defined by using cutoffs of ≥ 40, ≥ 50, and ≥ 50% positive cells, respectively, as reported in previous studies. 19,21,23,31,32 Flow cytometric immunophenotypic analysis was performed using 8-color flow cytometry. A FACScanto II or FACSCalibur cytometer (Becton-Dickinson Biosciences, San Jose, CA, USA) was used for analysis as described previously.…”

“…Previous studies have shown that patients with diffuse large B-cell lymphoma with MYC-R or MYC/BCL2 double hit have clinically aggressive disease and a poorer prognosis. 6,[10][11][12][13][14][15][16][17][18][19][20][21] Recent studies using immunohistochemical analysis have identified a subset of diffuse large B-cell lymphoma cases that express MYC and BCL2, known as double-positive lymphoma or double expresser lymphoma. Dual expression of MYC and BCL2 (MYC+/BCL2+) has been shown to be associated with a worse prognosis in patients with de novo diffuse large B-cell lymphoma treated with R-CHOP.…”

Frontline treatment of diffuse large B‐cell lymphoma: Beyond R‐CHOP

“…DA‐EPOCH‐R as first‐line treatment significantly reduced the risk of progression compared with R‐CHOP . Multivariable analyses, however, have not shown that DA‐EPOCH‐R improves OS compared with the standard R‐CHOP . A recent phase II study (NCT01092182) confirmed that DA‐EPOCH‐R produces durable remission in patients with MYC‐rearranged aggressive B‐cell lymphomas with EFS and OS of 71% and 76.7% respectively, at a median follow‐up of 55 months.…”