Incidence and Prognostic Impact of Secondary Neoplasia after High Dose Therapy Supported By Autologous Stem Cell Transplantation in Follicular Lymphoma. a Long Term Follow-up Analysis from the Geltamo Registry

Background:High dose therapy supported by autologous stem cell transplantation (HDT/ASCT) has been a treatment frequently indicated in follicular lymphoma (FL) patients and has contributed to modify the natural history of the disease. Secondary neoplasia is one of the concerns after HDT/ASCT, although its incidence after transplant-free treatments is considerable (RummelM et al. Lancet Oncol 2016; Sacchi S et al. Haematologica 2008). The high incidence of secondary neoplasia in some of the studies, together with the lack of OS advantage in transplanted patients compared to those treated with conventional Chemo/R, has led to abandon HDT/ASCT by many groups. However, its incidence is very variable among studies due in part to cohort different in terms of age, pre-ASCT treatments, used of TBI-based or TBI-free conditioning regimen or length of follow-up. Methods:The Incidence of secondary neoplasia, the factors associated with its development and the survival of 655 FL patients reported to the Spanish GELTAMO registry and intensified with HDT/ASCT between 1989 and 2007 with a median follow-up of 12.3 years from HDT/ASCT and 14.5 years from diagnosis were analyzed. Baseline characteristics and therapeutic-related data are listed in the table. Standardized Incidence Ratios (SIR) were calculated to assess the risk of a second malignancy by dividing the number of observed second malignancies with the number of expected sex matched incidence using the 2008 crudes rates in the Spanish population (J Farley et al. EJC 2013). Data were updated with a cut-off date of 31 June 2016. Results:Median OS were 21.3 years from HDT/ASCT and 22.6 years from the time of FL diagnosis. A total of 83 patients (12.75%) developed 85 second malignancies. There were 45 cases of solid tumors (51%), including 8 skin cancers; 34 cases of Acute Myeloid Leukemia or Myelodysplastic Syndromes (AML/MDS) (40%); 2 Acute Lymphoblastic Leukemia (ALL), 1 chronic myeloid leukemia (CML), 1 Hodgkin lymphoma (HL) and 2 cases of other cancers. The accumulated incidence at 5, 10 and 15 years were 6.7%, 12% and 17.8%, respectively. The incidence for solid tumors and AML/SMD were 2.1%, 4.1%, 9.5% and 3.1%,6.4% and 8,1% at 5, 10 and 15 years, respectively. Median time from HDT/AST to the diagnosis of the second malignancy was 5.5 years (IQR 3.2-9.6). Solid tumors and AML/SMD were documented with a median time of occurrence since HDT/ASCT 7.7 years (IQR 3.2-9.9) and 4.2 years (IQR 1.7-7.3), respectively. The SIR for second neoplasia was 2.8 (CI 95%: 2.6-2.9) and only 1.4 (CI 95% 1.3-16) in the case of solid tumors. Only male sex (P=.006) and the use of anthracycline at first line therapy in the case of solid tumors (P=.02) were associated with an increased number of second neoplasia. Older age and a status of disease before HDT/ASCT different to complete response showed a tendency. There were no differences according to the use of fludarabine or rituximab previously to HDT/ASCT, number of therapy lines before HDT/ASCT, time from diagnosis to HDT/ASCT or conditioning regimen. Median OS for patients with second neoplasia is 12 years from the time of FL diagnosis, 9.4 years from ASCT (fig 2)[14.5 y. for solid tumors and 8 y. for sMDS/sAML (P=.01)] and 1.5 years from the time of diagnosis of second neoplasia [2.3 y. for solid tumors and 1.25 y. for sMDS/sAML (P=.01)], respectively Conclusion: This very long follow-up study, that includes patients from the rituximab era, indicates that FL patients undergoing an ASCT are at an increased risk of developing a 2nd malignancy, especially AML-MDS. However, the incidence is not higher than the reported in other series without transplantation. Only male sex and the use of anthracyclines were associated with an increased risk of 2nd neoplasia. Given the favorable survival obtained by ASCT in FL, the risk of secondary neoplasia shouldn't preclude its application. However, once a neoplasia is diagnosed the prognosis is dismal. Thus, a carefully selection of patients candidates to HDT/ASCT is necessary. Table Table. Figure Figure. Disclosures Lopez-Jimenez: Abbvie: Membership on an entity's Board of Directors or advisory committees; Velgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; MundiPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Martín:Sevier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria.

Dose-Escalation with BEACOPP Escalated Is Superior to ABVD In the Combined-Modality Treatment of Early Unfavorable Hodgkin Lymphoma: Final Analysis of the German Hodgkin Study Group (GHSG) HD14 Trial

Abstract 765 Purpose: Combined modality treatment consisting of 4 cycles of chemotherapy and IF-RT is the standard treatment for early unfavorable HL. Overall survival (OS) and freedom from treatment failure (FFTF) at 5 years in this group of patients was 91% and 83%, respectively, in our prior HD8 study. Thus, the rationale for HD14 was to improve on these results by increasing dose intensity using BEACOPP escalated. Methods: Between January 2003 and July 2008, 1655 patients with histologically confirmed diagnosis of Hodgkin lymphoma in early unfavorable stages were randomized. Patients had to be 16–60 years old and have CS I, IIA with one of the following risk factors: large mediastinal mass (a), extranodal disease (b), elevated ESR (c), or ≥ 3 nodal areas (d), IIB with risk factors c or d). Patients were randomized to either 4 cycles of ABVD (arm A) or 2 cycles BEACOPP escalated followed by 2 cycles ABVD (arm B). All patients received 30Gy IF-RT after chemotherapy. Primary objective was the improvement of FFTF. Results: The full analysis set comprised 1623 patients (98.1%) who were documented and followed for treatment effects; 818 were in arm A and 805 in arm B. Patient characteristics were well balanced between the two arms with a median age of 33.6 years and most patients in stage IIA (67%). The overall response rate to treatment was 95% in each arm. With a median follow-up of 42.4 months, 20 patients had died in each arm; 19 patients in arm A had secondary neoplasia compared to 16 patients in arm B. Progressive disease was observed in 2.9% versus 0.9% of patients in arms A and B, respectively; early relapse rates were 2.8% versus 0.9%, and late relapse rates were 2.3% versus 0.9%. The estimated 4-year FFTF rate was 89.3% in arm A and 94.7% in arm B (p=0,0001, hazard ratio HR=2.04, 95%-CI: 1.39–2.94). There was no significant difference in overall survival yet (p=0.95). Acute grade III-IV toxicity rates of chemotherapy were higher in arm B (87.1%) than in arm A (50.7%) with leucopenia rates of 79% versus 24%, hair loss 48% versus 24%, thrombocytopenia 22% versus 0.1% and anemia 9% versus 1% in arms B and A respectively. 7.3% of patients had grade III/IV infections in arm B as compared to 3.4% in arm A. However, we observed no differences in treatment-related death or secondary neoplasia rates between treatment arms. Conclusion: Intensifying treatment for patients with early unfavorable HL using 2 cycles of BEACOPP escalated followed by 2 × ABVD and IFRT results in a significant improvement in tumor control as compared to our prior standard of 4 × ABVD plus IFRT. As defined in the study protocol, this more aggressive treatment was implemented as new standard of care for early unfavorable HL in our follow-up study (GHSG HD17). Disclosures: Greil: Cephalon: Research Funding.

Considerations about ocular neoplasia of dogs and cats

Primary and secondary neoplasia of dogs and cats may assume several different forms. Clinical signs are varied, and are manifest in accordance with the diseased tissue. The present article aims to review clinical and pathophysiologic aspects of frequent neoplasms that affect by the eye and the adnexal ocular structures of dogs and cats.

Long Term Follow up of Hairy Cell Leukemia (HCL) Patients (PTS) Treated with Interferon-Alpha (IFN-α). The Importance of Maintenance.

HCL is a chronic B-cell lymphoproliferative disorder with a specific morphology and immunophenotype of the malignant lymphocytes. Although purine analoges are the recommended first-line treatment, they are associated with significant immune suppression and secondary neoplasia. IFN-α is an alternative treatment with fewer long term side effects and considerable efficacy. AIM: The analysis of HCL patients treated with IFN-α as first-line therapy in a single Hematology Unit. PATIENTS AND METHODS: 75 consecutive pts diagnosed and followed in our Department between 1980 and 2005, treated with IFN-α were analyzed. RESULTS: 77.3% were males and their median age was 51 years (30–81). 57% had splenomegaly and 12% hepatomegaly at diagnosis. Their median hemoglobin was 11.3g/dL (4.5–14.3), their median leukocyte and absolute neutrophil counts were 3.1×109/L (0.9–26) and 0.77×109/L (0.03–3.9), respectively. Their median platelet count was 79×109/L (20–295). 33% had hypergammaglobulinemia and their median percentage of bone marrow infiltration at diagnosis was 75%. 10% of the pts were splenectomized before IFN-α treatment. The median time from diagnosis to IFN-α initiation was 0.7 months. The majority of pts (68%) received IFN-α induction at a dose of 3MU/day, while 15% 3MU every other day. Median duration of IFN-α induction was 23.5 months. 8% of pts achieved a complete response with a negative bone marrow, while 73% had a partial remission with a >50% reduction of bone marrow infiltration and a complete restoration of all blood counts. The median time to complete hematologic restoration was 10.7 months. 79% of pts received IFN-α maintenance, the majority of whom (58%) at a dose of 3MU/week. 69% of pts never needed a 2d line treatment, while among those who did, 65% were retreated with IFN-α. The 10-year overall survival was 80%. There were 2 cases of secondary neoplasia. At last follow-up 9% of pts were dead due to unrelated causes, 3% due to 2ary neoplasia, while none died due to disease. Two factors were of prognostic significance for freedom from 2d treatment (FF2T). FF2T was significantly longer for pts older than 51 years old (p<0.0004) and for those receiving IFN-α maintenance compared to those who did not (p<0.03). CONCLUSIONS: IFN-α has significant efficacy in HCL with a slow but sustained response. Continuous maintenance seems to be important in maintaining response. Younger patients might benefit less from IFN-α.

Gamma knife radiosurgery and its possible relationship to malignancy: a review

✓ The question has been raised recently whether gamma knife radiosurgery (GKS) can induce secondary neoplasia. Because there is little or no detailed knowledge about this potential complication, background information culled from the radiotherapy literature is reviewed as a guide to the clinical situations in which radiotherapy may induce secondary neoplastic change. Available case reports are then reviewed and discussed against the background of the current knowledge. On the basis of the review, the following suggestions are proposed on how to limiting the extent of this complication, document its frequency, and inform patients. It should be remembered that: the benefits of GKS are great; its alternatives also have risks; there often are no alternatives to GKS; follow-up documentation should be pursued more actively so that, if possible, no patient falls through the net; practitioners should be proactive in defining the problem, and genetic analysis of tumor biopsy specimens obtained in patients who will undergo or have undergone GKS should become routine; the extent of secondary neoplasia is not known; and patient information should be guided by what is known rather than by what is feared.