- Email: [email protected]
HHV-8-positive multicentric variant of Castleman disease
Abstracts factor for transplantation. HSCs mobilization, harvest and engraftment periods were evaluated. Material and Methods: One hundred and eight relapsed or refractory NHL cases treated with aHSCT in Ege University Hospital between 2008-2014 were evaluated retrospectively in terms of type of disease, sex, HSCs number, platelet and neutrophil engraftment period and outcomes based on our hospital records. Results: The median age of the patients was 53.2 years (19-76 years), and of 66 (61.1%) males and 42 (38.9%) females. Sixty-six (61.1%) of the patients were diffuse large B cell lypmhoma (DLBCL), 17 were (15.7%) mantle cell lyphoma (MCL), 10 (9.2%) were lymphoblastic lymphoma (LL), 10 (9.2%) were folicular lymphoma (FL), 4 (3.7%) were marginal zone lymphoma (MZL) and one (0.9%) was mycosis fungoides. All the patients were mobilised after a salvage chemotherapy regimen (ICE or ESHAP) combined with 10mg/kg/day dose of filgrastim. Mean collection day after filgrastim administration was 6.4 days for female and 6.1 for male. Mean apheresis cycle was 2.4 for female and 2.5 for male. Mean total CD34+ HSCs number was 8.7x106 for female and 7.9 x106 for male. Poor mobilization was not observed in any patient. There was no statistically difference between sex, mobilisation regimen and type of lymphoma in terms of HSCs collection day, total apheresis cycle and total CD34+ HSCs number. Mean neutrophil and platelet engraftment time was 12.1 and 15.6 days, respectively. Neutrophil and platelet engraftment times were 12,0 and 14,8 vs 12,2, 16,8 days for male and female, respectively. There was no statistically difference between sex in terms of neutrophil engraftment time but platelet engraftment time is statistically delayed in female patients (p<0.05). Transplantation related mortality was 0.8%, complete and partial remission after Ahsct was obtained in 52 (48%) and 25(23%) of patients, respectively. Overall survival was significantly better in patients with complete remission (p<0.05). Conclusion: High-dose chemotherapy, followed by aHSCT, is an effective treatment option for patients with relapsed/refractory Non-Hodgkin’s lyphoma, allowing further consolidation of response.
2008 to January 2013. The EPOCH regimen was: etoposide 50 mg/m2/d, vincristine 0.4 mg/m2/d, doxorubicin 10 mg/m2/d given together as CIV, days 1-4; cyclophosphamide 750mg/m2 IV on day 5; prednisone 60 mg/m2/d po days 1-5. Nine patients had PTCLNOS (60%); 4 had AITL (27%); 3 had ALCL ALK-negative (20%). Median age at diagnosis was 63 years (range 38-84). Nine patients were >60 years old (60%), 12 patient had IPI score >3. One patient with PTCL-NOS was HIV positive; 5 patients had EBV detectable in serum by PCR or tumor by immunohistochemistry (33%). Patients received a median of 6 EPOCH cycles (range 2-6). They were seen at least every 3 weeks or as clinically indicated. PET/CT scans were done pre-therapy, after cycle 3 and at end of therapy. Results: Common toxicities included neuropathy (27%), fatigue/anemia (40%), and nausea/vomiting (40%). Three patients required dose reduction or discontinuation of vincristine due to grade 3-4 neuropathy; 2 patients received 25% dose reduced etoposide in at least 2 cycles due to unrelated renal dysfunction. One patient died after cycle 2 from sudden cardiac death. Of 14 patients evaluable for response, 12 achieved complete remission (CR, 85%), 2 had refractory or progressive disease (RD/PD, 15%). One patient with PD died from disease after 3 cycles of EPOCH. Of 12 patients who achieved CR, 7 received consolidation with autologous HSCT. Nine out of 12 patients remained in CR at a median follow up of 21 months (range 6-39). After a median follow of 17 months (range 3-49) median progression free and overall survival were not reached. In univariate analysis, age > 60, ECOG performance status >2, IPI score>3, EBV status were not significantly related to worse outcomes. Discussion: In this small cohort, toxicities and disease response were comparable to historical CHOP data. Most of patients achieved durable CR. EBV association was not indicative of a worse prognosis. Interestingly, patients with IPI>3, ECOG>2, or age >60 did not have statistically worse outcomes. In conclusion, EPOCH resulted in durable responses and warrants further investigation in comparison to CHOP in PTCL.
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A Single Institution Experience with EPOCH in Peripheral T-cell Lymphomas (PTCL)
HHV-8-positive multicentric variant of Castleman disease
Marcello Rotta, MD, Bradley M. Haverkos, MD, MPH, Susan Geyer, Ph.D, Julianna Roddy, PharmD, Pierluigi Porcu, MD
E.K. Egorova, Hunan L. Julhakyan, A.L. Kovrigina, A.L. Melikyan National Research Center for Hematology, Moscow, Russian Federation
Ohio State University
Introduction: To date, CHOP remains the most common upfront treatment regimen for the treatment of PTCL. A retrospective subset analysis of German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) prospective trials suggested an improvement in event free survival (EFS) when etoposide was added to CHOP (CHOEP), in patients <60 years old (3-year EFS: 75.4% vs 51.0%, P 0.003) (Schmitz et al. Blood 2010). At Ohio State University, we have used an etoposide-containing regimen, EPOCH, as front line regimen for PTCL since 2008. Methods: We report on 15 patients with PTCL treated with EPOCH from April
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Clinical Lymphoma, Myeloma & Leukemia September 2015
Context: Castleman disease (CD) is rare lymphoproliferative disorder with local lesions with morphological picture (hyaline vascular, plasma cell or mix cell) and multicentric Castleman disaese (MCD), usually with plasma cell or mix cell morphology. In a separate group was include patients with HHV-8-positive MCD due to its extremely aggressive course and a high risk of transformation into HHV-8-positive plasmablastic lymphoma. Objective: The aim of this research work was to explore the clinical and morphological features HHV-8-positive MCD. Patients: In Hematological Center since 1996 to the present time observed clinical and morphological features of 87 patients with CD.
Abstracts Immunohistochemical examination revealed DNA HHV-8 lymph nodes tissue in patients with plasma cell and mix cell morphology. Results: In 45 patients were diagnosed plasma cell or mix cell variant CD: in 21, 8% local, in 29, 9% MCD. Immunohistochemistry with LANA HHV-8 antigen performed in 13 case local and in 21 generalized lesions. HHV- 8 identified only in six (28.6 %) cases MCD: five male and one female with median age 48, 2 years (range 36-77). The median follow-up was 39.2 months (3.3 years). In four cases were diagnosed mixed cell variant CD and in two cases plasma cell variant CD. In all cases detected constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly. There were various laboratory changes but the most significant were anemia, leukocytosis, leukopenia, thrombocytopenia, hypergammaglobulinemia, M-component, increased ESR and circulating immune complexes. In two cases of HHV-8-positive MCD was combined with autoimmune hemolytic anemia and in two cases with non-Hodgkin’s lymphoma. Two patients are alive after CHOP and R-CHOP therapy with rituximab maintenance. Two patients died of uncontrolled autoimmune hemolysis against the backdrop of long-term use of prednisone. Another patient died in the fourth year of the disease, after numerous cycles of chemotherapy by transformation into plasmablastic lymphoma. Moreover, 78 y.o. female died of kidney failure after one cycle CHOP chemotherapy. Conclusions: HHV-8-positive MCD proceeds with aggressive multiorgan lesions, pronounced changes in laboratory tests and characterized by unfavorable prognosis with a high risk of transformation in plasmablastic lymphoma and lethal outcome. Timely chemotherapy in patients with HHV-8-positive MCD can achieve remission and prolong life. Keywords: Castleman disease, multicentric Castleman disease, herpesvirus 8 types, plasmablastic lymphoma.
Retrospective, single-center, diagnosis after February 1, 2010. Setting: Tertiary referral center. Patients: R-CHOP-ineligible patients with DLBCL treated with R-CEOP. Interventions: R-CEOP (etoposide: 50mg/m2 IV D1, 100mg/m2 PO D2-3) x 6 cycles. Main Outcomes Measures: PFS, OS, and toxicity of R-CEOP overall and in relation to COO. Results: 26 patients with a median (range) age of 82 (61-91) years were treated. Patient characteristics included male: 65%, B symptoms: 35%, Stage 3-4: 65%, extranodal disease: 73%, bulky disease: 15%, ECOG PS > 1: 35%, and IPI scores 3-5: 58%. 32% of patients had a LVEF < 50%. Overall response rate was 75% with CR in 58% and PR in 17% of patients. At a median follow-up of 19 months, 2-year PFS and OS rates were 49% and 59%, respectively. COO (non-GCB vs. GCB) was significantly associated with PFS (HR ¼ 6.90, 95%CI ¼ 1.4532.81, P ¼ 0.015). 2-year PFS rates in non-GCB and GCB patients were 26% and 85%, respectively. COO was also significantly associated with OS (non-GCB vs. GCB: HR ¼ 4.91, 95% CI ¼ 1.00-24.34, P ¼ 0.05). The most common grade 3-4 toxicities were infection (23%), anemia (23%), and febrile neutropenia (19%). There was one treatment-related death due to infection. Conclusions: Patients with non-GCB DLBCL have a dismal prognosis with R-CEOP. In contrast, R-CEOP results in excellent outcomes in GCB DLBCL. This differential effect may be explained by the effect of topoisomerase II inhibitors on BCL-6, a known proto-oncogene with prognostic significance in GCB DLBCL. These results suggest R-CEOP is a safe and effective alternative to R-mini-CHOP in frail or older patients with GCB subtype DLBCL. Keywords: diffuse large B-cell lymphoma, elderly, etoposide, cell of origin, R-CEOP.
918 917 Outcomes with R-CEOP for R-CHOP-ineligible patients with diffuse large B-cell lymphoma are highly dependent on cell of origin Armin Rashidi,1 Eunhye Oak,1 Kenneth R. Carson,1 Nina D. Wagner-Johnston,1 Friederike Kreisel,2 Nancy L. Bartlett1 1
Division of Oncology, Washington University School of Medicine, St.
The experience of diagnostic and treating splenic diffuse red pulp lymphoma Hunan L. Julhakyan,1 L.S. Al-Radi,1 T.N. Moiseeva,1 K.I. Danishyan,1 A.M. Kovrigina,1 S.M. Glebova,1 S.A. Lugovskaya,2 V.N. Dvirnik,1 A.N. Khvastunova,3 I.A. Yakutik,1 V.G. Savchenko1 1
Hematological Scientific Center, Moscow, Russian Federation;
2
Russian Medical Academy of postdiplomic education, Moscow, Russian Federation; 3Federal scientific center of pediatric hematology and immunology, Moscow, Russian Federation
Louis, MO; 2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Context: The anthracycline component of R-CHOP can cause significant toxicity in frail older patients with diffuse large B-cell lymphoma (DLBCL) or those with underlying cardiac dysfunction. R-CEOP is an alternative regimen with doxorubicin replaced by etoposide. Outcomes with R-CEOP for R-CHOP-ineligible patients with DLBCL have not been previously reported for different cells of origin (COO) by Hans criteria: germinal center B-cell (GCB) versus non-germinal center. Objective: PFS and OS in R-CHOP-ineligible DLBCL patients treated with R-CEOP. Secondary Objective prognostic significance of COO. Design:
Context: WHO 2008 classification highlighted a new nosology e splenic diffuse red pulp lymphoma (SDRPL) with clinical and laboratory features similar both splenic marginal zone lymphoma and with hairy cell leukemia (HCL) and variant form of HCL (V-HCL). Experience of hematologists on diagnosis and differential diagnosis of SDRPL is extremely limited. Objective: The aim of our report is to characterize the clinical and immunomorphological features of splenic diffuse red pulp lymphoma on our own observations. Patients: During 2013-2014 years in National Research Center for Hematology were analyzed 87 spleen specimens removed in various B-cell lymphomas. In four (4.6%) cases the diagnosis SDRPL was made based on morphological, immunohistochemical,
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2008 to January 2013. The EPOCH regimen was: etoposide 50 mg/m2/d, vincristine 0.4 mg/m2/d, doxorubicin 10 mg/m2/d given together as CIV, days 1-4; cyclophosphamide 750mg/m2 IV on day 5; prednisone 60 mg/m2/d po days 1-5. Nine patients had PTCLNOS (60%); 4 had AITL (27%); 3 had ALCL ALK-negative (20%). Median age at diagnosis was 63 years (range 38-84). Nine patients were >60 years old (60%), 12 patient had IPI score >3. One patient with PTCL-NOS was HIV positive; 5 patients had EBV detectable in serum by PCR or tumor by immunohistochemistry (33%). Patients received a median of 6 EPOCH cycles (range 2-6). They were seen at least every 3 weeks or as clinically indicated. PET/CT scans were done pre-therapy, after cycle 3 and at end of therapy. Results: Common toxicities included neuropathy (27%), fatigue/anemia (40%), and nausea/vomiting (40%). Three patients required dose reduction or discontinuation of vincristine due to grade 3-4 neuropathy; 2 patients received 25% dose reduced etoposide in at least 2 cycles due to unrelated renal dysfunction. One patient died after cycle 2 from sudden cardiac death. Of 14 patients evaluable for response, 12 achieved complete remission (CR, 85%), 2 had refractory or progressive disease (RD/PD, 15%). One patient with PD died from disease after 3 cycles of EPOCH. Of 12 patients who achieved CR, 7 received consolidation with autologous HSCT. Nine out of 12 patients remained in CR at a median follow up of 21 months (range 6-39). After a median follow of 17 months (range 3-49) median progression free and overall survival were not reached. In univariate analysis, age > 60, ECOG performance status >2, IPI score>3, EBV status were not significantly related to worse outcomes. Discussion: In this small cohort, toxicities and disease response were comparable to historical CHOP data. Most of patients achieved durable CR. EBV association was not indicative of a worse prognosis. Interestingly, patients with IPI>3, ECOG>2, or age >60 did not have statistically worse outcomes. In conclusion, EPOCH resulted in durable responses and warrants further investigation in comparison to CHOP in PTCL.
915
916
A Single Institution Experience with EPOCH in Peripheral T-cell Lymphomas (PTCL)
HHV-8-positive multicentric variant of Castleman disease
Marcello Rotta, MD, Bradley M. Haverkos, MD, MPH, Susan Geyer, Ph.D, Julianna Roddy, PharmD, Pierluigi Porcu, MD
E.K. Egorova, Hunan L. Julhakyan, A.L. Kovrigina, A.L. Melikyan National Research Center for Hematology, Moscow, Russian Federation
Ohio State University
Introduction: To date, CHOP remains the most common upfront treatment regimen for the treatment of PTCL. A retrospective subset analysis of German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) prospective trials suggested an improvement in event free survival (EFS) when etoposide was added to CHOP (CHOEP), in patients <60 years old (3-year EFS: 75.4% vs 51.0%, P 0.003) (Schmitz et al. Blood 2010). At Ohio State University, we have used an etoposide-containing regimen, EPOCH, as front line regimen for PTCL since 2008. Methods: We report on 15 patients with PTCL treated with EPOCH from April
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Clinical Lymphoma, Myeloma & Leukemia September 2015
Context: Castleman disease (CD) is rare lymphoproliferative disorder with local lesions with morphological picture (hyaline vascular, plasma cell or mix cell) and multicentric Castleman disaese (MCD), usually with plasma cell or mix cell morphology. In a separate group was include patients with HHV-8-positive MCD due to its extremely aggressive course and a high risk of transformation into HHV-8-positive plasmablastic lymphoma. Objective: The aim of this research work was to explore the clinical and morphological features HHV-8-positive MCD. Patients: In Hematological Center since 1996 to the present time observed clinical and morphological features of 87 patients with CD.
Abstracts Immunohistochemical examination revealed DNA HHV-8 lymph nodes tissue in patients with plasma cell and mix cell morphology. Results: In 45 patients were diagnosed plasma cell or mix cell variant CD: in 21, 8% local, in 29, 9% MCD. Immunohistochemistry with LANA HHV-8 antigen performed in 13 case local and in 21 generalized lesions. HHV- 8 identified only in six (28.6 %) cases MCD: five male and one female with median age 48, 2 years (range 36-77). The median follow-up was 39.2 months (3.3 years). In four cases were diagnosed mixed cell variant CD and in two cases plasma cell variant CD. In all cases detected constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly. There were various laboratory changes but the most significant were anemia, leukocytosis, leukopenia, thrombocytopenia, hypergammaglobulinemia, M-component, increased ESR and circulating immune complexes. In two cases of HHV-8-positive MCD was combined with autoimmune hemolytic anemia and in two cases with non-Hodgkin’s lymphoma. Two patients are alive after CHOP and R-CHOP therapy with rituximab maintenance. Two patients died of uncontrolled autoimmune hemolysis against the backdrop of long-term use of prednisone. Another patient died in the fourth year of the disease, after numerous cycles of chemotherapy by transformation into plasmablastic lymphoma. Moreover, 78 y.o. female died of kidney failure after one cycle CHOP chemotherapy. Conclusions: HHV-8-positive MCD proceeds with aggressive multiorgan lesions, pronounced changes in laboratory tests and characterized by unfavorable prognosis with a high risk of transformation in plasmablastic lymphoma and lethal outcome. Timely chemotherapy in patients with HHV-8-positive MCD can achieve remission and prolong life. Keywords: Castleman disease, multicentric Castleman disease, herpesvirus 8 types, plasmablastic lymphoma.
Retrospective, single-center, diagnosis after February 1, 2010. Setting: Tertiary referral center. Patients: R-CHOP-ineligible patients with DLBCL treated with R-CEOP. Interventions: R-CEOP (etoposide: 50mg/m2 IV D1, 100mg/m2 PO D2-3) x 6 cycles. Main Outcomes Measures: PFS, OS, and toxicity of R-CEOP overall and in relation to COO. Results: 26 patients with a median (range) age of 82 (61-91) years were treated. Patient characteristics included male: 65%, B symptoms: 35%, Stage 3-4: 65%, extranodal disease: 73%, bulky disease: 15%, ECOG PS > 1: 35%, and IPI scores 3-5: 58%. 32% of patients had a LVEF < 50%. Overall response rate was 75% with CR in 58% and PR in 17% of patients. At a median follow-up of 19 months, 2-year PFS and OS rates were 49% and 59%, respectively. COO (non-GCB vs. GCB) was significantly associated with PFS (HR ¼ 6.90, 95%CI ¼ 1.4532.81, P ¼ 0.015). 2-year PFS rates in non-GCB and GCB patients were 26% and 85%, respectively. COO was also significantly associated with OS (non-GCB vs. GCB: HR ¼ 4.91, 95% CI ¼ 1.00-24.34, P ¼ 0.05). The most common grade 3-4 toxicities were infection (23%), anemia (23%), and febrile neutropenia (19%). There was one treatment-related death due to infection. Conclusions: Patients with non-GCB DLBCL have a dismal prognosis with R-CEOP. In contrast, R-CEOP results in excellent outcomes in GCB DLBCL. This differential effect may be explained by the effect of topoisomerase II inhibitors on BCL-6, a known proto-oncogene with prognostic significance in GCB DLBCL. These results suggest R-CEOP is a safe and effective alternative to R-mini-CHOP in frail or older patients with GCB subtype DLBCL. Keywords: diffuse large B-cell lymphoma, elderly, etoposide, cell of origin, R-CEOP.
918 917 Outcomes with R-CEOP for R-CHOP-ineligible patients with diffuse large B-cell lymphoma are highly dependent on cell of origin Armin Rashidi,1 Eunhye Oak,1 Kenneth R. Carson,1 Nina D. Wagner-Johnston,1 Friederike Kreisel,2 Nancy L. Bartlett1 1
Division of Oncology, Washington University School of Medicine, St.
The experience of diagnostic and treating splenic diffuse red pulp lymphoma Hunan L. Julhakyan,1 L.S. Al-Radi,1 T.N. Moiseeva,1 K.I. Danishyan,1 A.M. Kovrigina,1 S.M. Glebova,1 S.A. Lugovskaya,2 V.N. Dvirnik,1 A.N. Khvastunova,3 I.A. Yakutik,1 V.G. Savchenko1 1
Hematological Scientific Center, Moscow, Russian Federation;
2
Russian Medical Academy of postdiplomic education, Moscow, Russian Federation; 3Federal scientific center of pediatric hematology and immunology, Moscow, Russian Federation
Louis, MO; 2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Context: The anthracycline component of R-CHOP can cause significant toxicity in frail older patients with diffuse large B-cell lymphoma (DLBCL) or those with underlying cardiac dysfunction. R-CEOP is an alternative regimen with doxorubicin replaced by etoposide. Outcomes with R-CEOP for R-CHOP-ineligible patients with DLBCL have not been previously reported for different cells of origin (COO) by Hans criteria: germinal center B-cell (GCB) versus non-germinal center. Objective: PFS and OS in R-CHOP-ineligible DLBCL patients treated with R-CEOP. Secondary Objective prognostic significance of COO. Design:
Context: WHO 2008 classification highlighted a new nosology e splenic diffuse red pulp lymphoma (SDRPL) with clinical and laboratory features similar both splenic marginal zone lymphoma and with hairy cell leukemia (HCL) and variant form of HCL (V-HCL). Experience of hematologists on diagnosis and differential diagnosis of SDRPL is extremely limited. Objective: The aim of our report is to characterize the clinical and immunomorphological features of splenic diffuse red pulp lymphoma on our own observations. Patients: During 2013-2014 years in National Research Center for Hematology were analyzed 87 spleen specimens removed in various B-cell lymphomas. In four (4.6%) cases the diagnosis SDRPL was made based on morphological, immunohistochemical,
Clinical Lymphoma, Myeloma & Leukemia September 2015
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