MYC + diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation

Cuccuini, Wendy; Brière, Josette; Mounier, Nicolas; Voelker, Hans-Ullrich; Rosenwald, Andreas; Sundström, Christer; Cogliatti, Sergio; Hirchaud, Edouard; Ysebaert, Loïc; Bron, Dominique; Soulier, Jean; Gaulard, Philippe; Houlgatte, Rémi; Gisselbrecht, Christian; Thiéblemont, Catherine

doi:10.1182/blood-2012-01-406033

Cited by 147 publications

(121 citation statements)

References 22 publications

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“…Indeed, in 20-80% of cases of DLBCL and BCLU with a MYC breakpoint, there is an accompanying BCL2 and/or BCL6 breakpoint. [12][13][14][15][16] According to the World Health Organization (WHO) classification, lymphomas in which such a combination of a MYC break with a BCL2 break and/or a BCL6 break (fur- (DHL). 4 All other lymphomas with a MYC breakpoint, irrespective of the presence of other aberrations, are called "single-hit" lymphomas (SHL).…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nphomas. In BL the MYC translocation always involves one of the immunoglobulin loci (most commonly IGH, alternatively IGL or IGK) and is considered a disease-initiating event which occurs in the context of a rather simple karyotype. Indeed, the genomic complexity in BL is, overall, low. [6][7][8] In contrast, MYC translocations in other mature Bcell lymphomas frequently involve non-IG partners and are mostly found in complex karyotypes, often in addition to well-known primary aberrations including the IGH-BCL2 translocation.6,9-11 Consequently, they likely occur during disease progression rather than disease initiation. Indeed, in 20-80% of cases of DLBCL and BCLU with a MYC breakpoint, there is an accompanying BCL2 and/or BCL6 breakpoint. [12][13][14][15][16] According to the World Health Organization (WHO) classification, lymphomas in which such a combination of a MYC break with a BCL2 break and/or a BCL6 break (fur- (DHL). 4 All other lymphomas with a MYC breakpoint, irrespective of the presence of other aberrations, are called "single-hit" lymphomas (SHL). MYC breaks are seen in approximately 10% (3-17%) of all DLBCL and 15-20% of FL grade 3B, 17,18 representing on average a DHL in 50-60%. 14,[16][17][18][19][20] This also implies that the remaining 40-50% of MYC + lymphomas are "single-hit" and that their importance, despite this high percentage, might have been underappreciated. These lymphomas with MYC translocations, including DHL, have received increased attention because several studies showed them to run an aggressive clinical course. 9,11,21 However, gene expression and other molecular genetic data are scarce 3,22 and, consequently, the molecular make up of DHL and SHL other than BL remains largely unknown. Moreover, it is unclear in which pathological and molecular aspects DHL differs from SHL other than molecular Burkitt lymphoma (mBL).therIn that respect it should be noted that, in the presence or absence of a MYC break, oncogenes other than BCL2 and BCL6, including BCL3, chromosomal locus 9p13 (potentially affecting PAX5), CCNE1, as well as unknown partners involved in IGH breaks, can be deregulated through juxtaposition to one of the IG-loci. 16,[23][24][25][26] Breakpoints affecting both MYC and these genes might, therefore, also point to a DHL, although according to the WHO classification they are defined as SHL. 4 To investigate differences and similarities between SHL and DHL as well as between BCL2 + /MYC + and BCL6+ /MYC + DHL we explored the morphological, immunohistochemical, genetic and gene expression features of 80 adult MYC + mature aggressive B-cell lymphomas other than mBL. Methods Sample selection and pathology reviewAll lymphomas were investigated as part of the Molecular Mechanisms in Malignant Lymphomas (MMML) network project. The MMML protocols have been approved centrally by the institutional review board of the coordination center in Göttingen, Germany. All cases with an mBL gene expression signature (see Bioinformatica...

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma

et al. 2013

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“…On the other hand, there is also a report that salvage therapy with R-ICE and R-DHAP and autologous transplantation did not improve the PFS or OS in C-MYC-positive DLBCL [25]. Thus, this issue still remains controversial.…”

Section: Discussionmentioning

confidence: 88%

A Case of Advanced Primary Thyroid Double-Hit B Cell Lymphoma in Which Complete Remission has been Maintained After High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation Performed During the Second Remission, with a Review of the Literature

Sekiguchi

Shimada

Imai

et al. 2014

Indian J Hematol Blood Transfus

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“…However, most centers have opted not to offer myeloablative approaches to patients above the age of 50 irrespective of the performance status of the patient. As it is becoming increasingly apparent that certain subtypes such as MYC rearrangements carry bad prognosis independently from the known prognostic factors and regardless of the type of the treatment, 50 new approaches should be explored. Patients for example with relapsed responsive disease and MYC mutations who might have been offered an autologous transplantation up till now, might become candidates for more aggressive upfront treatments including an allogeneic transplantation.…”

Section: Discussionmentioning

confidence: 99%

The role of allogeneic haematopoietic progenitor cell transplantation in patients with diffuse large B-cell non-Hodgkin lymphomas (DLBCL)

Papageorgiou

Cwynarski

Kottaridis

2013

Bone Marrow Transplant

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Despite the undoubted improvement in the prognosis of patients with diffuse large B-cell lymphomas (DLBCLs) with the addition of rituximab in the front-line treatment, a significant proportion of patients still relapse. Salvage immune-chemotherapy followed by high-dose therapy with autologous haematopoietic cell transplantation (auto-HCT) remains the treatment of choice for such patients, especially in those who demonstrate chemosensitive disease. In recent years, allogeneic haematopoietic cell transplantation (allo-HCT) has increasingly been used for patients who are resistant to salvage treatment or relapse after an auto-HCT. Strategies using reduced intensity conditioning regimens have allowed application of this approach to a broader range of patients. PFS is up to 55% with a risk of relapse up to 80% depending on different studies. In multivariate analysis, several factors have been associated with favourable outcome including chemosensitivity of the disease, younger age and Karnofsky performance status at the time of the transplant being the strongest ones. DLIs have shown to induce durable responses in relapsed or progressed disease; however, its role remains controversial as the results are inferior to the responses seen in other haematological malignancies. More recently, the addition of MoAbs in the non-myeloablative conditioning regimens has shown encouraging results. In conclusion, allo-HCT is a feasible option in selective patients with chemosensitive DBCL, as it reduces the risk of relapse; however, this is achieved at the cost of significant non-relapse mortality.

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MYC + diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation

Cited by 147 publications

References 22 publications

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma

A Case of Advanced Primary Thyroid Double-Hit B Cell Lymphoma in Which Complete Remission has been Maintained After High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation Performed During the Second Remission, with a Review of the Literature

The role of allogeneic haematopoietic progenitor cell transplantation in patients with diffuse large B-cell non-Hodgkin lymphomas (DLBCL)

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