bluuebunny/crossref_metadata_2025_split huggingface dataset:
CVP alternating with fludarabine (CVP/F) chemotherapy prior to idiotype vaccination for follicular lymphoma (FL)
Authors: Ai W. Z. , Hsu F. J. , Timmerman J. M. , Czerwinski D. , Taidi B. , Levy R. , Horning S. 
Published: March 2020

8065 Background: Reducing the tumor burden prior to vaccination facilitates an effective immune response (IR) against the idiotype in FL. In this context, we evaluated the efficacy and toxicity of a novel cytoreductive regimen, CVP/F. Methods: Newly diagnosed, advanced stage FL patients (pt) were treated with CVP (cyclophosphamide 400 mg/m2 PO d1–5, vincristine 2 mg d 1, prednisone 100 mg/m2 d1–5) alternating with F (25 mg/m2 IV d1–5) every 21 days for 2 cycles beyond best response (maximum 8). Pt judged to be cytoreduced adequately were vaccinated monthly × 5 with idiotype protein made from their FL. Results: Among 34 enrolled pt, median age was 45 years (yr), and FLIPI scores were: 18% low, 71% intermediate and 12% high. 38% pt had grade 1 and 62% had grade 2 FL. There were no toxic deaths or opportunistic infections. With 233 cycles (117 CVP and 116 F) given to 33 evaluable pt, neutropenic fever occurred in 7 cycles (3%). 20 cycles (17%) of CVP and 29 cycles (25%) of F were dose reduced for leukopenia. 18 pt (53%) achieved a CR (16) or CRu (2), and 13 pt (38%) had a PR. 22 pt (65%) treated with CVP/F proceeded to vaccination; 10 additional pt (29%) were vaccinated after secondary chemotherapy was given for further cytoreduction. At median follow-up of 11.2 yr, 15-yr overall survival (OS) was 85%. Two of 5 deaths occurred without lymphoma progression. TTF (time to treatment failure = second treatment, relapse, death) at 11 yr was 38%. Anti-idiotype antibody and T cell IR were seen in 44% and 31% pt, respectively. There were no differences in TTF or OS according to IR. Conclusions: CVP/ F was effective in advanced FL, comparing favorably with our historical experience with CVP in terms of CR rate, proportion proceeding to vaccination, TTF and OS after vaccination. This favorable outcome may have been due to the novel alternating CVP/F cytoreductive regimen, idiotype vaccination or both. The idiotype vaccine is now being tested in phase III trials. The CVP/F regimen also warrants further evaluation. No significant financial relationships to disclose.
Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders: BCL2 as a prognostic marker
Authors: Oton A. B. , Hong W. , Melhem M. , George D. , Foon K. , Ghobrial I. M. 
Published: March 2020

8073 Background: PTLD is the most serious hematological complications of solid-organ transplantation. We determined clinical and immunohistopathological prognostic factors for overall survival (OS) in patients with PTLD. Methods: Eighty-four patients with PTLD between 1980 and 2004 at University of Pittsburgh were identified. Immunohistochemistry staining was performed on tumor at diagnosis for BCL2, BCL6, cMYC, p53, PS6k, HSP90 and NFkB. Univariate associations between individual clinical and immunohistopathological features and OS were compared using Cox proportional hazard models. Survival curves were generated via the method of Kaplan-Meier. Results: The median age at the time of diagnosis of PTLD was 53 years. Thirty four percent of patients presented with early PTLD. Sixty-four percent of patients were EBV positive by in situ hybridization. Lung transplant was significantly related to grafted organ involvement (p=0.035). Lung and multiorgan transplants were associated with a higher risk for early PTLD (p=0.0033 and p=0.054), while renal transplant was associated with risk for late PTLD (p=0.0011). The median survival for all patients was 20.8 months, 95% CI: (7.4–77.6). On univariate analysis for OS, poor prognostic factors were identified: age of transplant >60 yr (p=0.02), multiorgan transplant (p=0.02), ECOG>2 (p<0.0001), grafted organ involvement and extranodal disease at the time of diagnosis (p<0.011), early PTLD (p<0.0001), and elevated white blood cell count (WBC) 1 month prior to diagnosis (p=0.01). Good prognostic factors included late PTLD, monomorphic disease, CD20 positive and rituximab use. Only BCL2 strongly correlated with prognosis (p=0.002). A final clinico-pathological model for survival was constructed using three factors: ECOG >2, elevated WBC one month prior diagnosis and BCL2 overexpression. Patients with these three risk factors had median survival of 10 days (95% CI: 0–41), in comparison with patients with none of these risk factors had median survival of 1,414 days. Conclusions: Patients who had 3 factors ECOG >2, elevated WBC one month prior diagnosis, and BCL2 overexpression in tumor tissue had worse median survival than the patients with none of these three factors. No significant financial relationships to disclose.
The utility of 18-F-fluorodeoxyglucose positron emission tomography in evaluation of bone marrow involvement by non-Hodgkin lymphoma (NHL)
Authors: Muslimani A. , Farag H. , Francis S. , Spiro T. P. , Daw H. A. , Chaudhry A. A. , Chan V. C. 
Published: March 2020

8077 Introduction: In NHL, the anatomic extent of the disease is an important factor influencing the overall survival. Clinically, NHLs are classified as indolent, aggressive, or highly aggressive. Bone marrow (BM) involvement is a sign of extensive disease, and iliac crest (IC) BM biopsy (BMB) is the established method for the detection of BM infiltration. However, IC BMB is associated with a high rate of false- negative result. We assess the ability of 18F-FDG PET scan to ascertain the presence of BM involvement in NHL. Methods: We retrospectively reviewed charts from January 2002 through November 2006 of histologically proven NHLs. 87 patients (pts) were eligible for our study (38 males, 49 females; age range 42–81 years). All pts were examined by whole-body 18F-FDG-PET scan for initial staging, and all had unilateral posterior IC BMB. BM involvement was established following the result of 1) unilateral posterior IC BMB, and 2) image-guided BMB following positive 18F-FDG-PET scan in selected patients. Results: Among the PET+ / IC BMB- group, 3 pts had a positive CT-scan guided BMB at the site of involvement detected by the 18F-FDG-PET scan (2 from the humerus,1 from the femur); the remaining 7 pts did not have a site-directed biopsy. Our data demonstrate an overall sensitivity of 0.76 for the PET scan detecting BM involvement in all pts and specificity of 0.88. We point out that the 0.88 specificity may be spuriously low, this is a result of the fact that of the 10 PET+ / IC BMB- pts 7 have not had directed biopsy to the site of involvement detected by the18F-FDG- PET-scan. Further analysis revealed no significant difference between the sensitivity (P = 0.21) and specificity (p = 0.99) between I- NHL and A/HA- NHL groups. Conclusion: 18F-FDG-PET scan shows potential to detect BM involvement in NHL. In particular, image-guided repeat BMB may be considered in pts with negative initial IC BMB, whose 18F-FDG-PET scan demonstrates BM involvement in a different site. No significant financial relationships to disclose. [Table: see text]
Gallium, rituximab, and dexamethasone for relapsed NHL
Authors: Smith S. E. , Wren K. , Stiff P. J. , Toor A. , Rodriguez T. , van Gestel D. 
Published: March 2020

8079 Background: Almost 50% of patients with intermediate grade non-Hodgkin's lymphomas (NHL) treated with standard CHOP- like therapy will have less than a complete response (CR) after treatment or will relapse after obtaining a CR. Salvage chemotherapy followed in responders by an autologous stem cell transplant (ASCT) can be curative. For many patients, this is not an option due to age, comorbidities, or lack of response. A non-cross resistant agent with activity in NHL which could salvage more patients is gallium nitrate Methods: We conducted a phase II clinical trial investigating the combination 3 non-myelosuppressive agents, gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. Gallium is given at 200mg/m2 CIV days 1–7, rituximab 375mg/m2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients had relapsed or refractory disease and had a SWOG PS ≤3. Patients may have failed prior ASCT or allogeneic SCT. This was a 2 stage, phase II study with initial evaluation after 22 patients of whom at least 10 responders were needed for completion of the study, as determined prior to start of trial Results: We enrolled 22 patients on study. 15 had large cell, 6 had transformed follicular and 1 had mantle cell NHL. Most of these patients were refractory to one or several prior salvage regimens [13/22 (59%)]; all had prior rituximab 22/22 (100%) and 18/22 (82%) had it with there most recent treatment. No patients developed grade 3 or 4 toxicities, except grade 4 lymphopenia in 7/22 (32%). The overall response rate was 10/22 (45%); CR/CRu 8/22 (36%); PR 2/22 (9%); SD 4/22 (18%); and PD 8/22 (36%). Five patients went on to receive stem cell transplant (including 3 allogeneic and 2 ASCT). Two of the responders were patients who had failed a prior stem cell transplant: 1 ASCT failure who remains in CR >18 months and an allograft failure in CR >14 months after relapse. Of the 22, 10 (46%) are alive at a median f/u of 17.2 months, of whom 7 are currently NED Conclusions: This regimen appears to be effective and relatively non-toxic for patients with relapsed and refractory NHL, including stem cell transplant failure. As CR at ASCT may be associated with an improved outcome, a trial of GaRD combined with RICE is planned to improve cytoreduction prior to ASCT in patients with relapsed NHL. No significant financial relationships to disclose.
CHOP compared to THP-COP regimen: Long-term outcome in Chinese non-Hodgkin lymphoma (NHL) patients
Authors: Zhai L. , Cheng C. , Niraula S. , Huang Y. , Li Z. M. , Wang S. S. , Huang H. Q. , Lin T. Y. 
Published: March 2020

8081 Background: THP-ADM (Pirarubicin) has potential to replace conventional ADM (Adriamycin) because of less severe toxicities. However, only a few studies have compared the long-term outcome between patients receiving the two drugs. A Japanese trial (JGTLE) shows the CR rate of THP-COP group was greater than CHOP group in elderly T-cell Non-Hodgkin's Lymphoma (NHL) patients. The current study was aimed at comparing the long-term outcome and toxicities between NHL patients receiving CHOP and THP-COP regimens within similar age-groups and pathological sub-types. Methods: 505 previously untreated NHL patients receiving either standard CHOP or THP-COP regimen (cyclophosphamide 750 mg/m2, doxorubicin or pirarubicin 50 mg/m2, vincristine 1.4 mg/m2and prednisone 40 mg/m2 for 5 days) were enrolled. Results: Patients’ characteristics between CHOP group(n=279) and THP-COP (n=228) group were well balanced. There were no differences in CR rate (54.8% vs. 54.0%, p=0.85) and response rate (82.1% vs. 84.1%, p=0.55). With a median follow-up of 59.7months, survival rate was similar (5-year OS: 56.7% vs. 55.8%, 5-year PFS: 43.5% vs. 47.3%, 5-year DFS: 54.0% vs. 54.7%). The incidence of cardiotoxicity(myocardial dysfunction and arrhythmia)was almost the same (10.0% vs10.2 %; P=0.958). Less Alopecia (39.1% vs. 28.8%, p= 0.015)and gastrointestinal toxicities(63.1% vs. 50.0%, p=0.003) were observed in THP-COP group. No differences between the two groups were observed within different pathological subtypes (B-cell subtype: CR rate 58.2% vs. 56.7%, 5-year OS 59.2% vs. 60.0%; T-cell subtype: CR rate 47.0% vs. 45.5%, 5-year OS 50.5% vs. 43.4%) and age-groups (<60 years group: CR rate 51.6% vs. 53.7%, p= 0.684; 5y OS 58.9% vs.61.1%, p= 0.570; =60 years group: CR rate 67.9% vs. 54.8 %, p= 0.148; 5y OS 48.0% vs. 42.1 %, p= 0.314). In the 33 elderly patients of T-cell subtype, CR rates were almost the same. (73.7% vs. 42.9%, p=0.073). Conclusions: The long-term outcome of NHL patients receiving THP-COP is similar to those receiving CHOP within similar age groups and pathologic subtypes. Cardiotoxicity occurs at a similar rate in both groups, while a lower incidence of alopecia and gastrointestinal toxicities was observed in THP-COP group. No significant financial relationships to disclose.
Allogeneic stem cell transplantation (allo-SCT) in T-cell lymphomas: A French national survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Authors: le Gouill S. , Milpied N. , Buzyn A. , Socié G. , Mothy M. , Vernant J. , Ifrah N. , Haioun C. , Michallet M. , Volteau C. , Blaise D. 
Published: March 2020

8095 Background: T- and NK-cell lymphomas represent 10–15% of non-Hodgkin's lymphoma in adults.Despite intensive chemotherapy including or not autologous stem cell transplantation upfront, a majority of patients experience relapse. Methods: We retrospectively analyzed T-cell lymphomas patients transplanted from a related or unrelated HLA identical sibling donor with myeloablative or non-myeloablative conditioning regimen. Patients younger than 15 years at the time of transplantation, HIV positive patients or lymphoblastic lymphomas were excluded. We present the results of this study based on the SFGM-TC data-base. At the present time, we analyzed 57 cases from 10 french centers. Results: Diagnosis was PTCL (n=19) , AITL (n=8), anaplastic large cell lymphoma (ALCL) (n=20), hepatosplenic γ/d lymphoma (n=2), T-cell granular lymphocytic leukemia (n=1) and localized nasal NK/T cell lymphoma (n=3), NK/T cell lymphoma (n=1), HTLV1 cell lymphoma (n=2) and enteropathy-associated T-cell lymphoma (n=1). There were 38 males and 19 females. Median age at diagnosis was 38 years (13 - 61 y). At diagnosis, 51 patients had IPI score > or = 3. Median time from diagnosis to transplantation was 12 months (4.6–17). All patients but 15 underwent myeloablative conditioning regimen. Source of stem cells was BMSC (n=38), peripheral stem cells (n=18) or cord blood (n=1). Transplantation was performed from a related HLA-matched sibling donor in 53 cases. Disease status at the time of transplantation was CR in 25 cases, PR in 19 cases and SD/PD/refractory in 13 cases. Eleven patients presented acute GVH grade 3/4. After transplantation, 91% of patients were in CR compared to 43 % before. Six patients experienced relapse and eighteen patients died because toxicity related mortality. Conclusions: Preliminary results show that allo-SCT is an attractive option in aggressive T-cell lymphomas and confirm the role of a graft versus T-cell lymphoma effect. Ongoing analysis will identify prognostic factors and be presented at the time of the meeting. The present study will provide usefull tools for clinicians to evaluate the role of allo-SCT in the specific field of adult T- cell lymphomas. No significant financial relationships to disclose.
Pegylated liposomal doxorubicin (PLD) as an alternative treatment of cutaneous T-cell lymphoma
Authors: Quereux G. , Khammari A. , Nguyen J. M. , Benmiloud M. , Dreno B. 
Published: March 2020

8096 Background: Therapy of cutaneous T-cell lymphoma (CTCL) at early stages consists of various modalities. The advanced or transformed stage of CTCL is treated by the CHOP regimen as standard chemotherapy; has a 40% response rate and relapses within 6 months in > 60% of pts. Methods: A prospective open multicentre Phase II study to evaluate the use of PLD as a CTCL therapeutic agent, with 25 pts, (59±12 years). Eligibility criteria: Pts with histologic proof of CTCL stage II to IV, unresponsive to at least 2 lines of therapy; transformed CTCL or non epidermotropic lymphoma CD30 + or CD30. PLD was administered i.v., 40 mg/m2 every 4 wks for 8 cycles. Objective of study was overall response rate (ORR); secondary objectives were safety, disease-free survival (DFS) and overall survival (OS). Results: Phase II study of 14pts with CTCL stage IIb/III, and 11pts with transformed CTCL, at baseline. Treatment duration was 8 cycles in 13 pts, 2–6 cycles in 10pts, and 2 pts were withdrawn during cycle 1 due to anaphylactic-like reactions. Among 23 treated pts, 5pts (22%) achieved a complete response (CR), 9pts (39%) a partial response (PR), with 61% ORR. DFS was 18 ± 4.5 mos; longest treatment duration was 24 mos. Median OS was 28 ± 3 mos. In general, PLD treatment was well tolerated. The main adverse events were grade 3 neutropenia (4%); grade 3 septicemia (8%) and 1 case of bilateral grade 3 pneumopathy. There were only 3 cases of grade 1 palmoplantar erythrodysesthesia. Conclusions: This is the first prospective multicentric study investigating activity and tolerance of 40 mg/m2 q28days of PLD in CTCL. The current study confirmed effectiveness of PLD(∼61%) in CTCL treatment, but did not show improved efficacy with dose increases (Wollina, Cancer, 2003). This data combined with Wollina’s data, support the use of PLD as a promising therapy in advanced stages of CTCL. The duration of response is superior to that achieved with CHOP. This has been confirmed in a small, trial, and needs to be confirmed in a larger trial. No significant financial relationships to disclose.
HLA class II alleles predict recurrence and pattern of failure in early-stage melanoma patients
Authors: Chun Y. S. , Wang Y. , Gershenwald J. E. , Ross M. I. , Johnson M. M. , Liu P. , Schacherer C. W. , Reveille J. D. , Lee J. E. 
Published: March 2020

8503 Background: Prior reports have suggested a link between specific HLA class II alleles, including HLA-DRB1*1101, and melanoma recurrence. We therefore investigated the relationship between HLA class II alleles and clinical outcome in a large population of patients who presented with localized melanoma. Methods: HLA class II alleles were determined by typing of genomic DNA from patients who presented with localized melanoma (AJCC stage IA-IIC). Patients found to have occult regional disease by sentinel node biopsy were excluded. Log-rank and Cox analysis of outcome versus standard prognostic factors and common HLA class II alleles (=5% of the population) was performed. Results: 1,241 patients underwent HLA typing. The median primary tumor thickness was 1.1 mm, 16% were ulcerated, and the median follow-up was 56 months. Tumor thickness, ulceration, and Clark level were independent predictors of recurrence. The HLA class II allele HLA-DRB1*1101 (11% of the population) independently predicted a higher risk of recurrence [hazard ratio (HR) 2.04, P=0.004] while HLA-DRB1*0401 (20% of the population) predicted a lower risk of recurrence (HR 0.42, P=0.004). HLA- DRB1*1101 was a particularly strong predictor of recurrence in stage I patients (HR 2.73, P<0.0001). Among patients who recurred, HLA- DRB1*1101 was an independent predictor of local-regional vs. distant recurrence (HR 2.7, P=0.007), and was more common in those whose first recurrence was isolated to the regional nodal basin, compared to those whose first recurrence was elsewhere or in multiple locations (24% HLA-DRB1*1101-positive vs. 14%, P<0.009). Conclusions: These results confirm that HLA-DRB1*1101 is a genetic marker of increased risk of melanoma recurrence, while HLA-DRB1*0401 is a marker of decreased risk of recurrence. HLA-DRB1*1101 is a particularly strong marker among the group of patients predicted clinically to be at the lowest overall risk for recurrence, and independently predicts pattern of recurrence (regional nodal failure). This information is of value in the development of surveillance strategies for melanoma patients, as well as the selection, stratification and randomization of early-stage melanoma patients for clinical trials. No significant financial relationships to disclose.
EORTC 18991: Long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma, final results of a randomized phase III trial
Authors: Eggermont A. M. , Suciu S. , Santinami M. , Kruit W. , Testori A. , Marsden J. , Punt C. , Hauschild A. , Gore M. , Keilholz U. 
Published: March 2020

8504 Background: EORTC 18991 is the largest adjuvant trial ever conducted in stage III melanoma. It assessed the efficacy and toxicity of long term PEG-IFN vs Observation (Obs.). Methods: PEG-IFN (Induction at 6μg/Kg/wk, sc, 8 weeks; followed by Maintenance at 3μg/Kg/wk, sc) for a total treatment duration of 5 years was compared to Obs. in 1256 patients (pts) with stage III melanoma (anyTN1–2M0 without in-transit metastases). Randomization was stratified for nodal involvement N1 (microscopic) vs N2 (palpable nodes), # of nodes, Breslow and ulceration of primary, sex and center. Distant Metastasis-Free Survival (DMFS) was the primary endpoint. Relapse-Free Survival (RFS) was the pre-specified regulatory primary endpoint. Overall survival (OS) was the secondary endpoint. Intent-to-treat analysis was performed. Results: Median follow-up was 3.8 yrs: HR = Hazard Ratio; NR = Not Reached In N1-pts (n=543) the benefit of PEG-IFN seemed more pronounced than in N2-pts (n=713): RFS (HR 0.73 p=0.02 and HR 0.86 p=0.12 for N1 and N2, respectively), DMFS (HR 0.75 p=0.03 and HR 0.94 p=0.53) and OS (HR 0.88 p=0.43 and HR 1.01 p=0.91). PEG-IFN therapy relative dose intensity (actual/planned dose while treated) reached median 88% (induction) and 83% (maintenance). 251 pts (40 %) stopped PEG-IFN because of toxicity. Grade 3–4 - mostly grade 3 - toxicities were reported in 45% (PEG-IFN), vs 12% (Obs.), including most frequently fatigue (15%), hepatotoxicity (10%) and depression (6%) with ECOG 0–1 Performance Status maintained in 83% of pts during maintenance. Conclusions: Long term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. Pts with only microscopic nodal involvement (Sentinel Node positive) seemed to have greater benefit in terms of both RFS and DMFS. Similar better effects of adjuvant IFN therapy in pts with lower disease burden are observed in 2 consecutive EORTC trials (18952 and 18991) involving 2644 pts. [Table: see text] [Table: see text]