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Low-Dose Total Marrow Lymphoid Irradiation (TMLI) for Donor Chimerism Before T-Replete Haploidentical Transplantation
E494
International Journal of Radiation Oncology Biology Physics
in RR, RFS or OS on multivariable analysis, our findings do not provide strong evidence for a clinically meaningful advantage for ChBC over TBI. Longer prospective follow-up of late effects and total transplantassociated costs is needed to inform the optimal choice between ChBC and TBI. Author Disclosure: S. Edelman: Stock; Johnson and Johnson, Vertex Pharmaceuticals, Abbott Laboratories, Abbvie Inc, Cytosorbents, Pfizer, Illiad Biotechnologies, GPB Scientific. E.K. Waller: None. M. Graiser: None. A.A. Langston: None. V. Dhere: None. J.L. Mikell: None. J.M. Switchenko: None. N. Esiashvili: None. M.K. Khan: None.
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3213 Langerhans Cell Histiocytosis (LCH) in the Modern Era: Excellent Local Control With Radiation Therapy (RT) B.H. Lok, M.R. Chelius, and J. Yahalom; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): To review clinical outcomes of LCH treated with RT at a large referral center in the modern era. Materials/Methods: We identified 248 patients (pts) with a histologically confirmed diagnosis of LCH presenting to our center from 20002015. We excluded 79 pts with limited follow up data and 24 pts with synchronous malignancies, leaving 145 pts. We reviewed their clinical and treatment characteristics. We used a single/multi-system (SS, MS, respectively) with or without risk organ (RO) involvement staging system, in addition to the Greenberger (GB) staging system [1]. ROs included hematologic, liver, and spleen for all pts, lung for pts <18y old, and CNS for pts 18y old. 33 lesions in 30 pts were irradiated, comprising the RT cohort. Response assessment per lesion included anatomic and metabolic imaging when available by the RECIST 1.1 and PERCIST 1.0 criteria, respectively. Overall survival (OS) and freedom from local failure (FFLF) were calculated by the Kaplan-Meier method. Chi-square and Wilcoxon rank-sum tests were performed to compare the RT and non-RT groups. Results: We found no significant differences in the demographics (age, gender, and race) and disease characteristics (GB and systembased/RO stage) of the RT cohort and non-RT cohort. We further examined the RT cohort. Median follow-up among the 30 RT pts was 4.9 yrs (range, 0.1-23.2), and 2.9 yrs (range, 0.01-14.6) from the date of initial biopsy and start of RT, respectively. Median age was 38.6 yrs (range, 1.5-65.7) where 30% of pts were <18 yrs old. Stage was SS in 80% and MS in 20%. Six pts had RO involvement, of which 5 were staged as MS. GB stage was 1a, 1b, and 2 in 50%, 10%, and 40%, respectively. From start of RT, 3- and 5-year OS was 85% and 78%, respectively. We analyzed the RT cohort per lesion irradiated. Median RT dose per lesion was 12 Gy (range 8-50.4) where 83% received 24 Gy. RT was delivered adjuvantly for 12 excised lesions (40%), of which 5 were complete excisions. IMRT/3DCRT was used for 16 lesions (53%), conventional photons for 8 (27%), electrons for 3 (10%), and indeterminate for 8 (27%) that were treated at an outside hospital. Two lesions lacked response documentation and were excluded from response analysis. RT response rates for 31 treated lesions were complete, partial, and stable in 52%, 39%, and 9%, respectively. One lesion relapsed in the RT field, and a second relapse occurred at RT field margin resulting in a 5-year in-field FFLF rate of 96% and overall FFLF rate of 92%. No Grade 3 or higher acute or late toxicities were observed. Conclusion: In the modern era, RT is a very effective treatment for LCH, providing high response rates, durable local control, and low toxicity rates. Further analysis will focus on additional comparisons between the RT and non-RT groups, including use of metabolic imaging and systemic therapy, and patient selection decisions for RT. [1] Greenberger, J. S., Crocker, A. C., Vawter, G., Jaffe, N., & Cassady, J. R. (1981). Results of treatment of 127 pts with systemic histiocytosis. Medicine, 60(5), 311e38. Author Disclosure: B.H. Lok: None. M.R. Chelius: None. J. Yahalom: None.
A Simplified 3-Isocenter Intensity Modulated Radiation Therapy for Craniospinal Irradiation to Minimize Planning and Treatment Time I. Takahashi,1 K. Kashiwado,2 A. Saito,1 Y. Takeuchi,1 I. Nishibuchi,1 Y. Murakami,1 T. Kimura,1 and Y. Nagata1; 1Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan, 2Hiroshima Red Cross and Atomic-Bomb Survivors Hospital, Hiroshima, Japan Purpose/Objective(s): Craniospinal irradiation (CSI) has become an important treatment method for central nervous system (CNS) relapse of hematological malignancies. However, conventional CSI planning is technically very challenging and field edge matching is needed because of the mechanical limitations of standard linear accelerators. We have developed a simple Linac-based IMRT technique for CSI and compared planning time, dose homogeneity and total treatment time with a conventional 3D-CRT technique. Materials/Methods: Fifteen patients with CNS relapse of hematological malignancies were treated with CSI using a novel IMRT technique and another fifteen patients underwent conventional 3D-CRT technique. A dose of 22.5 Gy in 15 fractions was prescribed. Planning target volume (PTV) included the whole brain and the spinal canal to the S3 vertebral level. Patient was positioned supine and immobilized using a thermoplastic facial mask and a vacuum positioning cushion. The IMRT plan used 3 field sets, each with a unique isocenter. One cranial field set involved 2 laterally opposed fields. Two spinal field sets used one posterioanterior (PA) field. Adjacent fields were overlapped, and cranial and spinal fields were optimized in a single plan. The 3D-CRT plan used edge-matching with moving junctions. Results: Comparing the IMRT plan with the 3D-CRT plan, the averaged simplified homogeneity index (HIZDmax/Dmin) of PTV was 1.22 0.06 and 1.46 0.09, respectively, the averaged V95 of PTV was 99.5 0.4% and 93.2 3.4%, respectively, the averaged planning time of three radiation oncologists was 40.1 4.9 minutes and 63.7 5.4 minutes, respectively and the averaged total treatment time (setup and beam-on times) was 32.5 4.3 minutes and 43.5 4.8 minutes, respectively. There were significant differences (P < 0.05). Short-term follow-up evaluations revealed no unexpected toxicity associated with the IMRT technique. Conclusion: We have developed a simplified 3-isocenter Linac-based IMRT approach for CSI. The dose to the brain and to the spine has been significantly improved, compared to the conventional 3D-CRT. The single IMRT plan is easier to plan and to manage. This new technique simplifies the set up and eliminates the need for shifting junctions during the course of CSI treatment and saves valuable time for patients with CNS relapse of hematological malignancies. Author Disclosure: I. Takahashi: None. K. Kashiwado: None. A. Saito: None. Y. Takeuchi: None. I. Nishibuchi: None. Y. Murakami: None. T. Kimura: None. Y. Nagata: None.
3215 Low-Dose Total Marrow Lymphoid Irradiation (TMLI) for Donor Chimerism Before T-Replete Haploidentical Transplantation P. Navarria, B. Sarina, L. Castagna, A. Rimondo, L. Morabito, P. Mancosu, A. Santoro, and M. Scorsetti; Humanitas Cancer Center, Rozzano, Italy Purpose/Objective(s): Nonmyeloablative (NMA) T replete haploidentical transplantation (TR-H) has been increasingly applied in high-risk hematologic patients when a HLA-matched donor was absent. Some data suggested that the outcome was similar to those obtained with matched related bone marrow transplantation, mainly in lymphoproliferative diseases. Recently, the Baltimore group reported a low dose TBI-based NMA regimen followed by T cell replete bone marrow, with post-infusion cyclophosphamide (Cy) to control graft versus host disease (GVHD) and graft rejection. The aims of the study were to evaluate the engraftment and chimerism of a NMA regimen containing low dose TMLI instead of TBI, in patients with advanced disease and bone marrow involvement.
Volume 96 Number 2S Supplement 2016 Materials/Methods: Since January 2009, patients received a TR-H at our institution. NMA or reduced intensity conditioning (RIC) regimen was used in 66 patients. For 12 patients (18%), TMLI (2 Gy) was used instead of TBI with advanced malignancies. The median age was 41 years (range 22-68). NMA consisted of fludarabine (30 mg/m2/day) on day -6 to -2, Cy (14.5 mg/kg/day) on days -6 and -5, total marrow and lymphoid irradiation (200 cGy in a single fraction) on day -1, followed by bone marrow or peripheral blood stem cell graft in all patients. Post engraftment immunosuppression consisted of Cy (50 mg/kg/day) on days +3 and +4, mycophenolate mofetil for 30 days, and tacrolimus or cyclosporine A. Results: Median age was 41y (22-68y). 50% had Hodgkin’s lymphoma. Immediate tolerance was good and no patients developed nausea or vomiting or parotid hyperplasia. No patients had oral mucositis. The median time to ANC >500/mL, and platelet recovery >20,000/mL was 22 and 30 days, respectively, and this was not different from data obtained with conventional low grade TBI (data not shown). Full donor chimerism was evident at day 30 in all evaluable patients (11/12). Two (17%) patients developed acute GVHD 2 and four (33%) patients developed limited chronic GVHD. Four of 12 (33%) died because of: PML, invasive lung aspergillosis, liver failure and pneumonia. Two (17%) patients died due to disease progression and 6 patients are alive in complete remission after a median follow-up time of 15 (2-25) months. Conclusion: This analysis suggests that TMLI could substitute conventional low dose TBI, with recipient immunosuppression, allowing engraftment and full donor chimerism. The mortality due to toxicity was felt to be due to poor patients’ characteristics. Author Disclosure: P. Navarria: None. B. Sarina: None. L. Castagna: None. A. Rimondo: None. L. Morabito: None. P. Mancosu: None. A. Santoro: None. M. Scorsetti: None.
3216 Prognostic Impact of Cell of Origin in Limited-Stage Diffuse Large B-Cell Lymphoma Treated With R-CHOP With or Without Radiation Therapy P. Youn, M.A. Cummings, S. Dhakal, W.R. Burack, C. Casulo, P.M. Barr, J.W. Friedberg, and L.S. Constine; University of Rochester Medical Center, Rochester, NY Purpose/Objective(s): Optimal treatment approaches for limited stage diffuse large B-cell lymphoma (DLBCL) are evolving in the rituximab-era, while understanding of the heterogeneity of the histologic subtypes of DLBCL continues to expand. In particular, the prognostic value of cell of origin (COO) in limited stage DLBCL is not clearly defined. We report our experiences with combined modality treatment of limited DLBCL with focus on the prognostic impact of COO subgroups. Materials/Methods: We retrospectively reviewed the records of patients who were diagnosed with limited stage de-novo DLBCL and treated in a single institution between January 2001 and December 2014. Characteristics including age, Ann Arbor clinical stage, extranodal disease, bulky disease (>7.5 cm), stage-modified International Prognostic Index (SMIPI), and immunohistochemistry were extracted. COO of germinal center B-cell-like (GCB) and non-GCB subtype was determined using the Hans algorithm. Results: Of 151 patients (median age of 62) included for the analysis, 46% (NZ69) were stage I and 54% (NZ82) were stage II. 54% (NZ81) had extranodal disease and 28% (NZ43) had bulky disease. Cell of origin was determined for 87 patients (62 GCB and 25 non-GCB). All patients were treated with R-CHOP, 50% (NZ76) receiving 4 or less cycles of chemotherapy. Consolidative RT was given to 58% (NZ87) of patients. Median follow-up from the time of diagnosis was 52 months (range 9-155 months). There were a total of 10 relapses and 21 deaths, with 5-year PFS of 91.7% and OS of 86.2%. There was no difference between RT and no RT groups (PZ0.64). Univariable and multivariable analyses controlling for SM-IPI, bulky disease, number of R-CHOP cycles, and RT showed that non-GCB origin was associated with worse outcomes. Patients with nonGCB DLBCL had inferior 5-year PFS (73.9% vs 95.9%, PZ0.03) and OS (59.7% vs 90.6%, PZ0.03) compared to GCB DLBCL. The trend of
Poster Viewing E495 inferior outcome in non-GCB DLBCL was more pronounced when 4 or less cycles of R-CHOP was given regardless of RT (logistic regression coefficient 3.1, PZ0.01). Conclusion: In the rituximab era, outcomes for limited stage DLBCL were excellent with or without consolidative RT. non-GCB DLBCL, however, are associated with poorer outcomes even in limited stage disease, especially when shorter course of R-CHOP was used. Further investigation on prognosis of limited stage Non-GCB DLBCL and optimal treatment approaches are warranted. Author Disclosure: P. Youn: None. M.A. Cummings: None. S. Dhakal: None. W.R. Burack: None. C. Casulo: None. P.M. Barr: None. J.W. Friedberg: None. L.S. Constine: None.
3217 A Multi-institutional Analysis of Consolidative Radiation Therapy Following Autologous Transplantation for Relapsed/Refractory Hodgkin Lymphoma S.A. Milgrom,1 S. Jauhari,2 J.P. Plastaras,3 J.N. Lukens,4 Y. Nieto,5 B. Dabaja,1 G.L. Smith,1 C.C. Pinnix,1 A. Maity,4 and S. Nasta6; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2Hospital of the University of Pennsylvania, Philadelphia, PA, 3Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 4 University of Pennsylvania, Philadelphia, PA, 5MD Anderson Cancer Center, Houston, TX, 6Division of Hematology / Oncology, University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): No consensus exists regarding the role of consolidative radiation therapy (RT) after autologous stem cell transplantation (SCT) for relapsed/refractory classical Hodgkin lymphoma (HL). We assessed its efficacy & toxicity in a multi-institutional analysis. We hypothesized that RT would improve disease control, with minimal toxicity. Materials/Methods: Eligible patients were 18 years old and underwent SCT from 2008-2015 for relapsed/refractory HL with a conditioning regimen of BCNU, cisplatin, and vincristine (BCV) or BCNU, etoposide, cytarabine, and melphalan (BEAM). Results: The cohort consisted of 161 patients from 2 institutions. Median age at SCT was 39 years. At initial diagnosis, 67% of patients had stage I/II HL, 89% received ABVD, and 29% received RT. Disease was primary refractory in 30% and relapsed in 70%. At progression/relapse, 64% of patients had disease limited to 1 side of the diaphragm, 6% had bulk, 30% had extranodal disease, and 15% had B symptoms. Patients received a median of 2 lines of chemotherapy (range 2-10). Conditioning for SCT was with BEAM for 64% and BCV for 36%. Median follow-up was 38 months after SCT (range 1-96). Twenty-two patients (14%) received RT within 4 months of SCT (median 3 months, range 1-4 months); in 21 (95%), RT was delivered after SCT. Median RT dose was 36 Gy (range 15-41.4 Gy). The table compares characteristics of patients who did vs. did not receive RT. At 3 years after SCT, overall survival (OS) was 81% and progression-free survival (PFS) was 64%. OS was associated with disease relapse both above & below the diaphragm (HR 2.5, P Z 0.01) and receipt of >1 line of salvage chemotherapy (HR 2.3, P Z 0.02). PFS was associated with disease relapse above & below the diaphragm (HR 1.7, P Z 0.04) and refractory disease (HR 1.6, P Z 0.07). RT was not associated with OS or PFS. 3-year OS was 100% for patients with relapsed disease who received RT (n Z 7), 82% for relapsed disease without RT (n Z 105), and 71% for
Abstract 3217; Table 1. Characteristic
RT (n [ 22)
No RT (n [ 139)
Stage I/II at Initial Diagnosis Stage I/II at Relapse Extranodal Disease at Relapse Relapsed vs. Refractory Disease Relapsed Primary Refractory Disease Status at SCT Complete Response Partial Response
16 (73%) 20 (91%) 2 (9%)
57 (42%) 83 (60%) 43 (31%)
0.01 0.004 0.04
7 (32%) 15 (68%)
104 (75%) 34 (25%)
<0.001
11 (50%) 11 (50%)
115 (83%) 23 (17%)
0.001
P
International Journal of Radiation Oncology Biology Physics
in RR, RFS or OS on multivariable analysis, our findings do not provide strong evidence for a clinically meaningful advantage for ChBC over TBI. Longer prospective follow-up of late effects and total transplantassociated costs is needed to inform the optimal choice between ChBC and TBI. Author Disclosure: S. Edelman: Stock; Johnson and Johnson, Vertex Pharmaceuticals, Abbott Laboratories, Abbvie Inc, Cytosorbents, Pfizer, Illiad Biotechnologies, GPB Scientific. E.K. Waller: None. M. Graiser: None. A.A. Langston: None. V. Dhere: None. J.L. Mikell: None. J.M. Switchenko: None. N. Esiashvili: None. M.K. Khan: None.
3214
3213 Langerhans Cell Histiocytosis (LCH) in the Modern Era: Excellent Local Control With Radiation Therapy (RT) B.H. Lok, M.R. Chelius, and J. Yahalom; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): To review clinical outcomes of LCH treated with RT at a large referral center in the modern era. Materials/Methods: We identified 248 patients (pts) with a histologically confirmed diagnosis of LCH presenting to our center from 20002015. We excluded 79 pts with limited follow up data and 24 pts with synchronous malignancies, leaving 145 pts. We reviewed their clinical and treatment characteristics. We used a single/multi-system (SS, MS, respectively) with or without risk organ (RO) involvement staging system, in addition to the Greenberger (GB) staging system [1]. ROs included hematologic, liver, and spleen for all pts, lung for pts <18y old, and CNS for pts 18y old. 33 lesions in 30 pts were irradiated, comprising the RT cohort. Response assessment per lesion included anatomic and metabolic imaging when available by the RECIST 1.1 and PERCIST 1.0 criteria, respectively. Overall survival (OS) and freedom from local failure (FFLF) were calculated by the Kaplan-Meier method. Chi-square and Wilcoxon rank-sum tests were performed to compare the RT and non-RT groups. Results: We found no significant differences in the demographics (age, gender, and race) and disease characteristics (GB and systembased/RO stage) of the RT cohort and non-RT cohort. We further examined the RT cohort. Median follow-up among the 30 RT pts was 4.9 yrs (range, 0.1-23.2), and 2.9 yrs (range, 0.01-14.6) from the date of initial biopsy and start of RT, respectively. Median age was 38.6 yrs (range, 1.5-65.7) where 30% of pts were <18 yrs old. Stage was SS in 80% and MS in 20%. Six pts had RO involvement, of which 5 were staged as MS. GB stage was 1a, 1b, and 2 in 50%, 10%, and 40%, respectively. From start of RT, 3- and 5-year OS was 85% and 78%, respectively. We analyzed the RT cohort per lesion irradiated. Median RT dose per lesion was 12 Gy (range 8-50.4) where 83% received 24 Gy. RT was delivered adjuvantly for 12 excised lesions (40%), of which 5 were complete excisions. IMRT/3DCRT was used for 16 lesions (53%), conventional photons for 8 (27%), electrons for 3 (10%), and indeterminate for 8 (27%) that were treated at an outside hospital. Two lesions lacked response documentation and were excluded from response analysis. RT response rates for 31 treated lesions were complete, partial, and stable in 52%, 39%, and 9%, respectively. One lesion relapsed in the RT field, and a second relapse occurred at RT field margin resulting in a 5-year in-field FFLF rate of 96% and overall FFLF rate of 92%. No Grade 3 or higher acute or late toxicities were observed. Conclusion: In the modern era, RT is a very effective treatment for LCH, providing high response rates, durable local control, and low toxicity rates. Further analysis will focus on additional comparisons between the RT and non-RT groups, including use of metabolic imaging and systemic therapy, and patient selection decisions for RT. [1] Greenberger, J. S., Crocker, A. C., Vawter, G., Jaffe, N., & Cassady, J. R. (1981). Results of treatment of 127 pts with systemic histiocytosis. Medicine, 60(5), 311e38. Author Disclosure: B.H. Lok: None. M.R. Chelius: None. J. Yahalom: None.
A Simplified 3-Isocenter Intensity Modulated Radiation Therapy for Craniospinal Irradiation to Minimize Planning and Treatment Time I. Takahashi,1 K. Kashiwado,2 A. Saito,1 Y. Takeuchi,1 I. Nishibuchi,1 Y. Murakami,1 T. Kimura,1 and Y. Nagata1; 1Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan, 2Hiroshima Red Cross and Atomic-Bomb Survivors Hospital, Hiroshima, Japan Purpose/Objective(s): Craniospinal irradiation (CSI) has become an important treatment method for central nervous system (CNS) relapse of hematological malignancies. However, conventional CSI planning is technically very challenging and field edge matching is needed because of the mechanical limitations of standard linear accelerators. We have developed a simple Linac-based IMRT technique for CSI and compared planning time, dose homogeneity and total treatment time with a conventional 3D-CRT technique. Materials/Methods: Fifteen patients with CNS relapse of hematological malignancies were treated with CSI using a novel IMRT technique and another fifteen patients underwent conventional 3D-CRT technique. A dose of 22.5 Gy in 15 fractions was prescribed. Planning target volume (PTV) included the whole brain and the spinal canal to the S3 vertebral level. Patient was positioned supine and immobilized using a thermoplastic facial mask and a vacuum positioning cushion. The IMRT plan used 3 field sets, each with a unique isocenter. One cranial field set involved 2 laterally opposed fields. Two spinal field sets used one posterioanterior (PA) field. Adjacent fields were overlapped, and cranial and spinal fields were optimized in a single plan. The 3D-CRT plan used edge-matching with moving junctions. Results: Comparing the IMRT plan with the 3D-CRT plan, the averaged simplified homogeneity index (HIZDmax/Dmin) of PTV was 1.22 0.06 and 1.46 0.09, respectively, the averaged V95 of PTV was 99.5 0.4% and 93.2 3.4%, respectively, the averaged planning time of three radiation oncologists was 40.1 4.9 minutes and 63.7 5.4 minutes, respectively and the averaged total treatment time (setup and beam-on times) was 32.5 4.3 minutes and 43.5 4.8 minutes, respectively. There were significant differences (P < 0.05). Short-term follow-up evaluations revealed no unexpected toxicity associated with the IMRT technique. Conclusion: We have developed a simplified 3-isocenter Linac-based IMRT approach for CSI. The dose to the brain and to the spine has been significantly improved, compared to the conventional 3D-CRT. The single IMRT plan is easier to plan and to manage. This new technique simplifies the set up and eliminates the need for shifting junctions during the course of CSI treatment and saves valuable time for patients with CNS relapse of hematological malignancies. Author Disclosure: I. Takahashi: None. K. Kashiwado: None. A. Saito: None. Y. Takeuchi: None. I. Nishibuchi: None. Y. Murakami: None. T. Kimura: None. Y. Nagata: None.
3215 Low-Dose Total Marrow Lymphoid Irradiation (TMLI) for Donor Chimerism Before T-Replete Haploidentical Transplantation P. Navarria, B. Sarina, L. Castagna, A. Rimondo, L. Morabito, P. Mancosu, A. Santoro, and M. Scorsetti; Humanitas Cancer Center, Rozzano, Italy Purpose/Objective(s): Nonmyeloablative (NMA) T replete haploidentical transplantation (TR-H) has been increasingly applied in high-risk hematologic patients when a HLA-matched donor was absent. Some data suggested that the outcome was similar to those obtained with matched related bone marrow transplantation, mainly in lymphoproliferative diseases. Recently, the Baltimore group reported a low dose TBI-based NMA regimen followed by T cell replete bone marrow, with post-infusion cyclophosphamide (Cy) to control graft versus host disease (GVHD) and graft rejection. The aims of the study were to evaluate the engraftment and chimerism of a NMA regimen containing low dose TMLI instead of TBI, in patients with advanced disease and bone marrow involvement.
Volume 96 Number 2S Supplement 2016 Materials/Methods: Since January 2009, patients received a TR-H at our institution. NMA or reduced intensity conditioning (RIC) regimen was used in 66 patients. For 12 patients (18%), TMLI (2 Gy) was used instead of TBI with advanced malignancies. The median age was 41 years (range 22-68). NMA consisted of fludarabine (30 mg/m2/day) on day -6 to -2, Cy (14.5 mg/kg/day) on days -6 and -5, total marrow and lymphoid irradiation (200 cGy in a single fraction) on day -1, followed by bone marrow or peripheral blood stem cell graft in all patients. Post engraftment immunosuppression consisted of Cy (50 mg/kg/day) on days +3 and +4, mycophenolate mofetil for 30 days, and tacrolimus or cyclosporine A. Results: Median age was 41y (22-68y). 50% had Hodgkin’s lymphoma. Immediate tolerance was good and no patients developed nausea or vomiting or parotid hyperplasia. No patients had oral mucositis. The median time to ANC >500/mL, and platelet recovery >20,000/mL was 22 and 30 days, respectively, and this was not different from data obtained with conventional low grade TBI (data not shown). Full donor chimerism was evident at day 30 in all evaluable patients (11/12). Two (17%) patients developed acute GVHD 2 and four (33%) patients developed limited chronic GVHD. Four of 12 (33%) died because of: PML, invasive lung aspergillosis, liver failure and pneumonia. Two (17%) patients died due to disease progression and 6 patients are alive in complete remission after a median follow-up time of 15 (2-25) months. Conclusion: This analysis suggests that TMLI could substitute conventional low dose TBI, with recipient immunosuppression, allowing engraftment and full donor chimerism. The mortality due to toxicity was felt to be due to poor patients’ characteristics. Author Disclosure: P. Navarria: None. B. Sarina: None. L. Castagna: None. A. Rimondo: None. L. Morabito: None. P. Mancosu: None. A. Santoro: None. M. Scorsetti: None.
3216 Prognostic Impact of Cell of Origin in Limited-Stage Diffuse Large B-Cell Lymphoma Treated With R-CHOP With or Without Radiation Therapy P. Youn, M.A. Cummings, S. Dhakal, W.R. Burack, C. Casulo, P.M. Barr, J.W. Friedberg, and L.S. Constine; University of Rochester Medical Center, Rochester, NY Purpose/Objective(s): Optimal treatment approaches for limited stage diffuse large B-cell lymphoma (DLBCL) are evolving in the rituximab-era, while understanding of the heterogeneity of the histologic subtypes of DLBCL continues to expand. In particular, the prognostic value of cell of origin (COO) in limited stage DLBCL is not clearly defined. We report our experiences with combined modality treatment of limited DLBCL with focus on the prognostic impact of COO subgroups. Materials/Methods: We retrospectively reviewed the records of patients who were diagnosed with limited stage de-novo DLBCL and treated in a single institution between January 2001 and December 2014. Characteristics including age, Ann Arbor clinical stage, extranodal disease, bulky disease (>7.5 cm), stage-modified International Prognostic Index (SMIPI), and immunohistochemistry were extracted. COO of germinal center B-cell-like (GCB) and non-GCB subtype was determined using the Hans algorithm. Results: Of 151 patients (median age of 62) included for the analysis, 46% (NZ69) were stage I and 54% (NZ82) were stage II. 54% (NZ81) had extranodal disease and 28% (NZ43) had bulky disease. Cell of origin was determined for 87 patients (62 GCB and 25 non-GCB). All patients were treated with R-CHOP, 50% (NZ76) receiving 4 or less cycles of chemotherapy. Consolidative RT was given to 58% (NZ87) of patients. Median follow-up from the time of diagnosis was 52 months (range 9-155 months). There were a total of 10 relapses and 21 deaths, with 5-year PFS of 91.7% and OS of 86.2%. There was no difference between RT and no RT groups (PZ0.64). Univariable and multivariable analyses controlling for SM-IPI, bulky disease, number of R-CHOP cycles, and RT showed that non-GCB origin was associated with worse outcomes. Patients with nonGCB DLBCL had inferior 5-year PFS (73.9% vs 95.9%, PZ0.03) and OS (59.7% vs 90.6%, PZ0.03) compared to GCB DLBCL. The trend of
Poster Viewing E495 inferior outcome in non-GCB DLBCL was more pronounced when 4 or less cycles of R-CHOP was given regardless of RT (logistic regression coefficient 3.1, PZ0.01). Conclusion: In the rituximab era, outcomes for limited stage DLBCL were excellent with or without consolidative RT. non-GCB DLBCL, however, are associated with poorer outcomes even in limited stage disease, especially when shorter course of R-CHOP was used. Further investigation on prognosis of limited stage Non-GCB DLBCL and optimal treatment approaches are warranted. Author Disclosure: P. Youn: None. M.A. Cummings: None. S. Dhakal: None. W.R. Burack: None. C. Casulo: None. P.M. Barr: None. J.W. Friedberg: None. L.S. Constine: None.
3217 A Multi-institutional Analysis of Consolidative Radiation Therapy Following Autologous Transplantation for Relapsed/Refractory Hodgkin Lymphoma S.A. Milgrom,1 S. Jauhari,2 J.P. Plastaras,3 J.N. Lukens,4 Y. Nieto,5 B. Dabaja,1 G.L. Smith,1 C.C. Pinnix,1 A. Maity,4 and S. Nasta6; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2Hospital of the University of Pennsylvania, Philadelphia, PA, 3Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 4 University of Pennsylvania, Philadelphia, PA, 5MD Anderson Cancer Center, Houston, TX, 6Division of Hematology / Oncology, University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): No consensus exists regarding the role of consolidative radiation therapy (RT) after autologous stem cell transplantation (SCT) for relapsed/refractory classical Hodgkin lymphoma (HL). We assessed its efficacy & toxicity in a multi-institutional analysis. We hypothesized that RT would improve disease control, with minimal toxicity. Materials/Methods: Eligible patients were 18 years old and underwent SCT from 2008-2015 for relapsed/refractory HL with a conditioning regimen of BCNU, cisplatin, and vincristine (BCV) or BCNU, etoposide, cytarabine, and melphalan (BEAM). Results: The cohort consisted of 161 patients from 2 institutions. Median age at SCT was 39 years. At initial diagnosis, 67% of patients had stage I/II HL, 89% received ABVD, and 29% received RT. Disease was primary refractory in 30% and relapsed in 70%. At progression/relapse, 64% of patients had disease limited to 1 side of the diaphragm, 6% had bulk, 30% had extranodal disease, and 15% had B symptoms. Patients received a median of 2 lines of chemotherapy (range 2-10). Conditioning for SCT was with BEAM for 64% and BCV for 36%. Median follow-up was 38 months after SCT (range 1-96). Twenty-two patients (14%) received RT within 4 months of SCT (median 3 months, range 1-4 months); in 21 (95%), RT was delivered after SCT. Median RT dose was 36 Gy (range 15-41.4 Gy). The table compares characteristics of patients who did vs. did not receive RT. At 3 years after SCT, overall survival (OS) was 81% and progression-free survival (PFS) was 64%. OS was associated with disease relapse both above & below the diaphragm (HR 2.5, P Z 0.01) and receipt of >1 line of salvage chemotherapy (HR 2.3, P Z 0.02). PFS was associated with disease relapse above & below the diaphragm (HR 1.7, P Z 0.04) and refractory disease (HR 1.6, P Z 0.07). RT was not associated with OS or PFS. 3-year OS was 100% for patients with relapsed disease who received RT (n Z 7), 82% for relapsed disease without RT (n Z 105), and 71% for
Abstract 3217; Table 1. Characteristic
RT (n [ 22)
No RT (n [ 139)
Stage I/II at Initial Diagnosis Stage I/II at Relapse Extranodal Disease at Relapse Relapsed vs. Refractory Disease Relapsed Primary Refractory Disease Status at SCT Complete Response Partial Response
16 (73%) 20 (91%) 2 (9%)
57 (42%) 83 (60%) 43 (31%)
0.01 0.004 0.04
7 (32%) 15 (68%)
104 (75%) 34 (25%)
<0.001
11 (50%) 11 (50%)
115 (83%) 23 (17%)
0.001
P