Pedro Reyes

Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy.

Background Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, showing improvement in disease-free survival (DFS) and overall survival (OS) rates in patients achieving pathological complete response (pCR). The relationship between immunohistochemistry-based molecular subtyping (IMS), chemo sensitivity and survival is currently a matter of interest. We explore this relationship in a Hispanic cohort of breast cancer patients treated with NAC. Methods A retrospective survival analysis was performed on Colombian females with breast cancer treated at Instituto de Cancerología-Clinica Las Américas between January 2009 and December 2011. Patients were classified according to immunohistochemistry-based subtyping into the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched, and triple-negative breast cancer. Demographic characteristics, recurrence pattern, and survival rate were reviewed by bivariate and multivariate analysis. Results A total of 328 patients fulfilled the study’s inclusion parameters and the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal B/HER2−: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile range: 31–52). Pathological response to NAC was as follows: complete pathological response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47 (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p = 0.01) and triple negative (p = 0.01). Conclusions pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours and non-pCR showed lower DFS.

Abstract C82: Carboplatin replacing BCNU in the BCNU, etoposide, cyclophosphamide (CVP) regimen for autologous stem cell transplant in patients with advanced lymphoma. Very low toxicity and encouraging results

Introduction: Autologous stem cell transplantation (ASCT) is the standard of care for treating patients with advanced lymphomas. The most commonly employed preparative regimens are BCNU (Carmustine), etoposide, cytosine arabinoside, melphalan (BEAM), and BCNU, etoposide, cyclophosphamide (CVP). Both regimens use BCNU, but this medication is associated with pulmonary toxicity, besides, in some underdeveloped countries there is a serious shortage of it. Carboplatin is an agent with good activity in Hodgkin and non-Hodgkin´s lymphomas and has a tolerable toxicity profile. Here we present our experience in a bone marrow transplant service in Colombia (South America) a country with shortage of BCNU. We evaluated the effects of a high-dose chemotherapy regimen with carboplatin replacing BCNU in the CVP regimen. Methods: After peripheral blood progenitor cells were mobilized with filgrastim 10 µg/kg for five days, twenty four patients with advanced lymphomas were conditioned prior to ASCT. The conditioning regimen consisted of carboplatin (450 mg/m2/ days -5,-4), etoposide (330 mgs mg/m2/days -4,-3,-2) and cyclophosphamide (2.000 mg/m2/days -3,-2,-1). After the autograft all patients received filgrastim or pegfilgrastim from day +5. Results: 24 consecutive patients were transplanted, median age 39.2 years (range 5-70), eleven were female. 11 patients (46%) had Hodgkin lymphoma; 7 in CR2 and four in partial remission or with refractory disease. 13 (54%) had non-Hodgkin´s lymphoma classified as: 6 diffuse large B cell, 5 mantle cell, 2 transformed follicular. Patients with mantle cell lymphoma were in CR1 while the rest were in CR2. The median CD 34+ cells infused was 4.09 x 106 cells/kg. The median time to achieve 500/µL absolute granulocyte count and 20.000/µL platelets was 11.7 days (range 8-17), and 16.5 days (range 7-23) respectively. 20 out of 24 had febrile neutropenia, the other toxicities were mild; grade II mucositis in three patients, neutropenic colitis in two and hemorrhagic cystitis in one. There were no pulmonary or renal toxicities and the transplant related mortality was 0%. The four patients with active disease achieved complete remission after transplant but two of them have relapsed. The one year overall survival is 100%, with a median follow-up of 12 months (range 5-18), and the disease-free survival, estimated by Kaplan-Meier is 90%. Conclusions: The use of carboplatin replacing BCNU in the CVP regimen seems to be a safe and effective conditioning protocol followed by ASCT in patients with various types of lymphomas. This treatment option seems an adequate alternative for underdeveloped countries with shortage of BCNU. The regimen shows good anti-tumor activity, with a tolerable toxicity profile. These promising results must be confirmed with the inclusion of more patients and a longer follow-up. Citation Format: Miguel Gonzalez Velez, Amado Jose Karduss-Urueta, Rosendo Perez, Luis Rodolfo Gomez, Juan Alejo Jimenez, Pedro Alejandro Reyes, Ana Cardona, Liliana Hurtado, Hilda Deossa, Clara Fernandez. Carboplatin replacing BCNU in the BCNU, etoposide, cyclophosphamide (CVP) regimen for autologous stem cell transplant in patients with advanced lymphoma. Very low toxicity and encouraging results. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C82.

Autologous Peripheral Blood Stem Cell Transplant Using BEAM or CBV without Cryopreservation. 82 Procedures in Patients with Relapsed Hodgkin and Non- Hodgkinxs Lymphoma

exact and Cochran-Mantel-Haenszel tests were used to compare responses and toxicities. Results: The median age of the patients was 58 yrs (range: 39-72) in Group A and 58 yrs (range: 49-68) in Group B. Group A had more female pts (56% vs 25%) and a decreased baseline renal function (median creatinine clearance 76 vs 108 ml/min) compared to Group B. There was no significant difference in disease status pre-2nd ASCT between the 2 groups. Salvage therapywas given to 12 pts in group A and 16 pts in group B. The median time between 2 ASCTs were 29 (range: 3-67) months in group A vs 35.5 (range: 18-58) months in group B. All patients received stem cells which were collected and cryopreserved prior to the 1stASCT. At day +100, seven patients from Group B had CR compared to 2 from group A (p1⁄4.11) (Table 1). Patients who received BEAM had higher incidence of febrile neutropenia (16 vs 10 pts) and longer hospitalization (23 vs 15 days, p <.0001). Other toxicities were not significantly different between these groups. Conclusion: BEAM seems to be a viable and tolerable conditioning regimen for 2ndASCT in MM pts. Further analyses including PFS and OS are planned to better define the two groups.

305: Irradiation of cellular blood components with cobalt 60 is very efficient and safe in the prevention of transfusion associated graft versus host disease (TA-GVHD) in the allogeneic transplant setting

For the prevention of TA-GHVH in patients who received a allogeneic stem cell transplant is mandatory the gamma irradiation of the all cellular blood components. This irradiation is usually done with Cesium 137 and with a special blood bank irradiators. However these devices are expensive; because that, in developing countries, is frequent the utilization of Cobalt 60 and the same device that is used in the radiotherapy department, instead of blood bank irradiators. We present our experience with this technique. From Dec 2002 to Dec 2005 thirty patients received a allogeneic stem cell transplant and 28 were analysed. The stem cells source was: peripheral blood 25, unrelated cord blood 2, and bone marrow 1. The irradiation of the blood was performed with Cobalt 60–1.24 Mev- (theratron 780 C); the irradiation field was calculated for covering all of the bag surface and a dose of 3.5 Gy was administered to the mild plane of the bag. 158 blood concentrates were transfused, 68 red cell (X:2.5 per patient), and 90 platelets (3.2 per patient). The pre transfusion median hemoglobin and platelet levels were 7.63 g/dl and 12.000/ul; after transfusion was a median increase of 2.3 gm/dl (0.6–4.7) in hemoglobin and 18.000/ul (0–140.000) in platelets. There was no any case of TA-GVHD. Four patients developed pos transplant aGVHD, in all of the cases the disease began 50 days or more after the last transfusion, there were no pancytopenia and the aGVHD was resolved completely with the treatment. Conclusion In receptors of allogeneic stem cell transplant the gamma irradiation of blood components with Cobalt 60 and with the same device which is used for patients radiotherapy is 100% effective and safe in the prevention of TA-GVHD. This is a good alternative in centers without blood bank irradiator