Background. Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin’s lympoma. Approximately half of all patients (pts) will be cured of their disease by primary therapy the remaining die of the disease. Gene-expression profiling in DLCBL has brought an insight into the biological heterogeneity of the disease. Two major subgroups were identified: germinal centre B (GCB) cell or non-germinal centre (non-GCB). In some recent papers the GCB group showes a significantly better survival than the non-GCB group. Immunohistochemistry has been evaluated as a surrogate for this molecular classification. Aims. The aim of this study was to define retrospectively the B-cell origin of 40 pts treated with R-CHOP14 and to evaluate if the dose-dense immuno-chemotherapy could improve their clinical outcome. Methods. We performed a centralized immunohistochemical stains on formalin-fixed paraffin-embedded tissues from diagnostic biopsies with the following antibodies: CD10, bcl-6, bcl-2, MUM1 and Mib1. Based on the algorithm published by Hans et al. we subdivided the patients in GCB origin and non-GCB origin. We evaluated also the prognostic value of single protein expression. Results. Twenty-seven pts were male and 13 female, 18 were stage I-II and 22 stage III-IV, 17 presented symptoms at diagnosis and 17 showed bulky disease. Twenty-two pts showed abnormal LDH value, the IPI was intermediate-high risk or high risk in 13 pts. According to immunohistochemistry analysis 16 pts derived from germinal centre and 24 from non-germinal centre, 12 pts presented a positive CD10, 30 a positivity for bcl6, 19 a positive bcl2 and 27 a positive MUM1. Twenty-nine pts (73%) obtained a complete remission (CR), 8 a partial response (PR) and 3 were non responders (NR). Four out 29 CR pts experienced relapse, three (75%) derived from non-germinal centre. Eight pts died, 4 derived from GCB and 4 from non-GCB. After a median period of observation of 16 months (range 3-70 months) the overall survival (OS) was 75% and the failure free survival (FFS) was 57%. The statistical analysis was performed comparing the B cell origin and clinical characteristics, moreover was also evaluated the expression of bcl2 either in GCB or in non-GCB lymphomas. In univariate analysis normal beta2 microglobulin and low-intermediate risk IPI were significantly associated with longer overall survival. In univariate and multivariate analysis FFS was significantly higher in low and low-intermediate IPI risk patients it was the only factor that influenced the FFS. No differences were reported in OS and FFS evaluating the B cell origin. Conclusions. In conclusion even if few patients were evaluated we can point out that the intensification could enhance the efficacy of R-CHOP regimen improving the overall survival and FFS in patients with non-GCB lymphoma. In this analysis the only significance was the IPI index that affected either OS or FFS. Further analysis with larger sample sizes of DLBCL patients are needed to verify this preliminary observations.
DOSE-DENSE THERAPY (R-CHOP14) SEEMS TO OVERCOME THE NEGATIVE PROGNOSTIC SIGNIFICANCE OF B CELL ORIGIN IN DLBCL LYMPHOMA PATIENTS / L., Rigacci; Martelli, Maurizio; B., Puccini; S., Di Lollo; E., Finolezzi; L., Nassi; M., Doria; R., Alterini; V., Carrai; A., Bosi. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 93 (SUPPL. 1):(2008), pp. 394-394. (Intervento presentato al convegno 13th Congress of the European-Hematology-Association tenutosi a Copenhagen, DENMARK nel JUN 12-15, 2008).
DOSE-DENSE THERAPY (R-CHOP14) SEEMS TO OVERCOME THE NEGATIVE PROGNOSTIC SIGNIFICANCE OF B CELL ORIGIN IN DLBCL LYMPHOMA PATIENTS
MARTELLI, Maurizio;
2008
Abstract
Background. Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin’s lympoma. Approximately half of all patients (pts) will be cured of their disease by primary therapy the remaining die of the disease. Gene-expression profiling in DLCBL has brought an insight into the biological heterogeneity of the disease. Two major subgroups were identified: germinal centre B (GCB) cell or non-germinal centre (non-GCB). In some recent papers the GCB group showes a significantly better survival than the non-GCB group. Immunohistochemistry has been evaluated as a surrogate for this molecular classification. Aims. The aim of this study was to define retrospectively the B-cell origin of 40 pts treated with R-CHOP14 and to evaluate if the dose-dense immuno-chemotherapy could improve their clinical outcome. Methods. We performed a centralized immunohistochemical stains on formalin-fixed paraffin-embedded tissues from diagnostic biopsies with the following antibodies: CD10, bcl-6, bcl-2, MUM1 and Mib1. Based on the algorithm published by Hans et al. we subdivided the patients in GCB origin and non-GCB origin. We evaluated also the prognostic value of single protein expression. Results. Twenty-seven pts were male and 13 female, 18 were stage I-II and 22 stage III-IV, 17 presented symptoms at diagnosis and 17 showed bulky disease. Twenty-two pts showed abnormal LDH value, the IPI was intermediate-high risk or high risk in 13 pts. According to immunohistochemistry analysis 16 pts derived from germinal centre and 24 from non-germinal centre, 12 pts presented a positive CD10, 30 a positivity for bcl6, 19 a positive bcl2 and 27 a positive MUM1. Twenty-nine pts (73%) obtained a complete remission (CR), 8 a partial response (PR) and 3 were non responders (NR). Four out 29 CR pts experienced relapse, three (75%) derived from non-germinal centre. Eight pts died, 4 derived from GCB and 4 from non-GCB. After a median period of observation of 16 months (range 3-70 months) the overall survival (OS) was 75% and the failure free survival (FFS) was 57%. The statistical analysis was performed comparing the B cell origin and clinical characteristics, moreover was also evaluated the expression of bcl2 either in GCB or in non-GCB lymphomas. In univariate analysis normal beta2 microglobulin and low-intermediate risk IPI were significantly associated with longer overall survival. In univariate and multivariate analysis FFS was significantly higher in low and low-intermediate IPI risk patients it was the only factor that influenced the FFS. No differences were reported in OS and FFS evaluating the B cell origin. Conclusions. In conclusion even if few patients were evaluated we can point out that the intensification could enhance the efficacy of R-CHOP regimen improving the overall survival and FFS in patients with non-GCB lymphoma. In this analysis the only significance was the IPI index that affected either OS or FFS. Further analysis with larger sample sizes of DLBCL patients are needed to verify this preliminary observations.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.