Summary
Primary breast diffuse large B‐cell lymphoma (DLBCL) is a rare subtype of non‐Hodgkin lymphoma (NHL) with limited data on pathology and outcome. A multicentre retrospective study was ...undertaken to determine prognostic factors and the incidence of central nervous system (CNS) relapses. Data was retrospectively collected on patients from 8 US academic centres. Only patients with stage I/II disease (involvement of breast and localized lymph nodes) were included. Histologies apart from primary DLBCL were excluded. Between 1992 and 2012, 76 patients met the eligibility criteria. Most patients (86%) received chemotherapy, and 69% received immunochemotherapy with rituximab; 65% received radiation therapy and 9% received prophylactic CNS chemotherapy. After a median follow‐up of 4·5 years (range 0·6–20·6 years), the Kaplan–Meier estimated median progression‐free survival was 10·4 years (95% confidence interval CI 5·8–14·9 years), and the median overall survival was 14·6 years (95% CI 10·2–19 years). Twelve patients (16%) had CNS relapse. A low stage‐modified International Prognostic Index (IPI) was associated with longer overall survival. Rituximab use was not associated with a survival advantage. Primary breast DLBCL has a high rate of CNS relapse. The stage‐modified IPI score is associated with survival.
We previously reported that remission duration < 1 year, extranodal disease, and B symptoms before salvage chemotherapy (SLT) can stratify relapsed or refractory Hodgkin lymphoma (HL) patients into ...favorable and unfavorable cohorts. In addition, pre-autologous stem cell transplant (ASCT) 18FDG-PET response to SLT predicts outcome. This phase 2 study uses both pre-SLT prognostic factors and post-SLT FDG-PET response in a risk-adapted approach to improve PFS after high-dose radio-chemotherapy (HDT) and ASCT. The first SLT uses 2 cycles of ICE in a standard or augmented dose (ICE/aICE), followed by restaging FDG-PET scan. Patients with a negative scan received a transplant. If the FDG-PET scan remained positive, patients received 4 biweekly doses of gemcitabine, vinorelbine, and liposomal doxorubicin. Patients without evidence of disease progression proceeded to HDT/ASCT; those with progressive disease were study failures. At a median follow-up of 51 months, EFS analyzed by intent to treat as well as for transplanted patients is 70% and 79%, respectively. Patients transplanted with negative FDG-PET, pre-HDT/ASCT after 1 or 2 SLT programs, had an EFS of > 80%, versus 28.6% for patients with a positive scan (P < .001). This prospective study provides evidence that the goal of SLT in patients with Hodgkin lymphoma should be a negative FDG-PET scan before HDT/ASCT. The study was registered at www.clinicaltrials.gov as NCT00255723.
To identify prognostic factors for patients transplanted for relapsed or refractory Hodgkin lymphoma we carried out a combined analysis of patients followed prospectively on 3 consecutive protocols ...at Memorial Sloan-Kettering Cancer Center. One hundred fifty-three patients with chemosensitive disease after ICE (ifosfamide, carboplatin, and etoposide)–based salvage therapy (ST) proceeded to high-dose chemoradiotherapy followed by autologous stem cell transplantation (ASCT). Patients were evaluated with computed tomography and functional imaging (gallium or fluorodeoxyglucose-positron emission tomography) prior to ST and again before ASCT. Functional imaging status before ASCT was the only factor significant for event-free survival (EFS) and overall survival by multivariate analysis and clearly identifies poor risk patients (5-year EFS 31% and 75% for FI-positive and negative patients respectively). Administration of involved-field radiotherapy with ASCT was marginally significant for EFS (P = .055). Studies evaluating novel STs, conditioning regimens, post-ASCT maintenance, or allogeneic stem cell transplantation are warranted for patients who fail to normalize pre-ASCT functional imaging.
Micro-Abstract Hepatosplenic T-cell lymphoma is a rare form of non-Hodgkin lymphoma, which carries a poor prognosis. We report our single-institution experience in the management of hepatosplenic ...T-cell lymphoma (HSTCL)- in 14 patients (pts) among whom 7 who remain alive (50%) and in remission at a median follow-up of 66 months. More frequent long-term survival was seen in those treated with a non-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) induction and consolidative stem cell transplant (SCT).
Summary
Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early ...relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan‐Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event‐free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post‐transplant maintenance strategies.
Micro-Abstract Peripheral T-cell lymphomas (PTCLs) are aggressive lymphomas without standard treatment. We retrospectively identified 65 patients with PTCL initially treated with the intention to ...perform autologous (HD-ASCT) or allogenic (allo-HSCT) stem cell transplant in the first complete remission (CR). Treatment with allo-HSCT and HD-ASCT had overall survival (OS) at 4 years of 66% and 67%, respectively. Baseline International Prognostic Index (IPI) score and interim response to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) might also predict outcome.
Abstract 2015▪▪This icon denotes a clinically relevant abstract
We previously reported the prognostic impact of pre-transplant functional imaging (FI) on outcome following autologous stem cell ...transplant (ASCT) for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) (Moskowitz AJ, et al. Blood 2010). This analysis was based upon patients treated on 3 consecutive Memorial Sloan-Kettering Cancer Center (MSKCC) clinical trials from 1994 to 2003. The cohort included patients evaluated by gallium or FDG-PET and the 5 year event free survival (EFS) for patients with normal vs abnormal pre-transplant FI was 75% and 31% respectively. Based upon these results, our treatment program has focused on the use of FDG-PET to determine eligibility for ASCT. While determination of FI results in our series was based upon visual interpretation, we now aim to investigate whether semi-quantitative evaluation of pre-transplant FDG-PET could better distinguish favorable and less favorable cohorts.
Patients with rel/ref HL treated on MSKCC clinical trials who underwent pre-salvage and pre-transplant evaluation with FDG-PET were included in this analysis. Pre-salvage and pre-transplant FDG-PET reports were reviewed and maximum SUV values for each scan were recorded. The delta-SUV was a calculation of the percent change in maximum SUV between pre-salvage and pre-transplant FDG-PET. EFS was calculated using the Kaplan-Meier method. The prognostic impact of FDG-PET results by visual interpretation and semi-quantitative interpretation was evaluated using the log-rank test.
One hundred and thirty nine patients with rel/ref HL treated on consecutive MSKCC clinical trials from October 2000 through August 2010 were evaluated. Of the 139 patients, 104 (75%) achieved FDG-PET normalization prior to ASCT. The median follow-up for survivors was 6 years. The 6 year EFS for FDG-PET negative and FDG-PET positive patients was 79% and 53% respectively (p<0.001, figure 1). Among the patients with abnormal pre-transplant FDG-PET, the median maximum SUV value was 4.3 and the median delta-SUV was 60%. We tested absolute pre-transplant maximum SUV values of 2, 3, 4, and 5 and we were unable to find a value of prognostic significance among FDG-PET positive patients. We tested delta-SUV values of 50%, 60%, 63%, 66%, and 72.9%. Patients with positive pre-transplant FDG-PET and ≥63% delta-SUV were found to have similar outcomes as patients with negative pre-transplant FDG-PET (p=.47, figure 2). The 6 year EFS for delta-SUV ≥63% patients was 77% compared to 44% for delta-SUV < 63% (p=0.12).
For rel/ref HL patients undergoing ASCT, semi-quantitative evaluation of pre-transplant FDG-PET using delta-SUV of 63% identifies a favorable cohort among patients with positive pre-transplant FDG-PET. The difference in outcome for patients with ≥63% delta-SUV and < 63% delta-SUV was not statistically significant, however, likely due to the small number of FDG-PET positive patients in our series. Nevertheless, patients who achieve delta-SUV of at least 63% prior to ASCT achieved similar outcomes as those with negative pre-transplant FDG-PET. The prognostic significance of the 63% delta-SUV cutoff needs to be evaluated further in prospective studies. Display omitted
No relevant conflicts of interest to declare.
Abstract 792
We previously reported the use of a sequential treatment (tx) program, R-CHOP-14 x4 followed by ICE x3, results in an 80% 5-y PFS (JCO 2010; 28 (23): 3754–3761) but interim (int) ...FDG-PET-4 (FDG-4) scan did not predict outcome. Patients (pts) with a positive (pos) FDG-4 underwent biopsy (bx), of which 85% were negative (neg). There was no difference in PFS for pts with pos FDG-4 and a neg bx vs. FDG-4 neg. In an attempt to reduce false pos FDG-4, we changed the induction tx as well as the timing of FDG-4. In addition, we prospectively evaluated 18F−fluorothymidine (FLT)-PET to determine its value for int evaluation. Proliferative index (PI) < or ≥80% risk adapted the consolidation therapy.
Eligible pts were <70 yrs with advanced stage DLBCL, FL grade 3B or primary mediastinal large B-cell lymphoma (PMBL). Pre-treatment evaluation included contrast-enhanced CT, FDG-PET and FLT-PET. Induction t× consisted of R-R-CHOP-14 x3 and CHOP-21 ×1. FDG-4 was performed 17–20 days after cycle 4 of therapy and a b× performed if pos. Consolidation was risk-adapted: FDG-4 neg or b× neg: ICE −3 for PI <80% and augmented RICE ×2 for PI ≥ 80%. Pts with a pos b× were treated with augmented RICE × 2 followed by HDT/ASCR. Use of FLT-PET was exploratory. In the first cohort, FLT-PET was repeated after cycle 1, and in the second cohort after cycle 2. Int FDG-4 was interpreted using the Deauville criteria (value of 4 or 5 was pos). FLT-PET was interpreted visually (neg FLT = uptake decreased to < blood pool and background). Delta SUV was calculated for both tracers to provide standardization.
Sixty pts are evaluable; 50 underwent FLT-PET (10 pts could not be imaged due to lack of FLT availability or inability to schedule the test because of rapid tumor progression). Pt characteristics include: median age 54 (range 21–71), elevated LDH (82%); stage IV (75%); KPS <80 (25%) and age-adjusted (AA) IPI: low intermediate (LIR), HIR, and HR, 25%, 57% and 18% respectively. Pathology correlatives: PI ≥80 (35%); cell of origin (COO) via Hans model: GCB, ABC, PMBL, FL grade 3b: 42%, 33%, 22% and 3%, respectively. At median follow-up of 34 months for surviving pts, the PFS and OS are 79.3% and 85.6%, respectively. Pretreatment COO, AA-IPI, and PI were not predictive for PFS. The combination of altered induction therapy and timing of FDG-4 impacted on int evaluation. FDG-4 and int SUV max (>5) both predicted for PFS (p=.015 and .003, respectively). However, once again, pts with FDG-4 pos, bx neg evaluation had the same outcome as those with neg FDG-4 (p=.28) We combined the 2 FLT cohorts since the results were not significantly different. For the exploratory evaluation of FLT-PET, interpretation of FLT-PET-1/2 was based on delta SUV of >66% as a neg or favorable scan result. Thirty-three FLT-PET-1/2 scans were neg and 29 pts are progression-free (PF), including 8 pts with a pos FDG-4 (all had a negative bx and 7 are PF, hence 7 false pos FDG-4 scans). Among the 17 pts with pos FLT-PET-1/2, nine are PF. Nine FLT-PET-1/2 pos patients were FDG-4 neg and 7 are PF (hence improved response or false pos FLT). Lastly, pts with both pos FLT and FDG-4 did poorly; only 2 of 8 patients are PF.
These results confirm the excellent PFS of our sequential R-CHOP-14/ICE program. Altering the rituximab schedule, delaying int restaging by one week, as well as the use of FLT improved int evaluation. In this study, pts with a neg early FLT had an excellent outcome and likely no further imaging test is needed until the end of therapy for this cohort. In addition, pts with a neg FDG-4, despite a pos FLT, also did well with our induction/consolidation program. Future studies in these sub-groups may include reduced treatment strategies. Patients with dual tracer positive disease did poorly and the addition of novel therapy which may include kinase inhibitors with or without transplant is warranted. Display omitted
No relevant conflicts of interest to declare.
Abstract 3139▪FN2▪This icon denotes a clinically relevant abstract
Early stage, non-bulky (nb) classical Hodgkin lymphoma (cHL) patients receive intensive radiologic surveillance after completion of ...standard therapy despite a statistically low risk of relapse. This study sought to evaluate the relapse risk and value of radiologic surveillance in this subset of patients treated with 6 cycles of ABVD who achieve a PET negative complete remission (CR).
We identified all early-stage, nb cHL patients who were treated with 6 cycles of ABVD at MSKCC from 01/2002 to 12/2008. To be eligible for the study, patients had to have received an initial staging PET (from any institution) and an interim and/or post-treatment PET at MSKCC (or an associated facility) with ≥24 months follow-up or until evidence of treatment failure. Patients who received gallium scans were ineligible as were pediatric patients, patients with CD20+ positive cHL (as MSKCC data has shown this subset to have a statistically poorer prognosis compared to CD20 negative cHL receiving ABVD alone Portlock et al, 2004), composite lymphoma, multiple malignancies, known HIV infection, or refractory disease during 6 cycles of ABVD. All interim and post-treatment PETs were re-evaluated by two MSKCC nuclear medicine specialists (HS, RCL). Costs per scan for each patient during post-treatment surveillance were based upon standard, national Medicare reimbursements of $770/CT ($600 technical/$170 professional) and $1, 181/PET ($1, 042 technical including FDG/$139 professional) and multiplied according to the number of scans per type/per patient. Patient characteristics and imaging results during and after therapy were assessed and interpreted in relation to clinical outcome.
Forty-seven eligible patients were identified. The median age was 28 years (range: 17–65) and the majority were female (n =35/75%). Median follow-up was 55 months. Most patients presented with stage IIA disease (n= 34/72%) and were of favorable risk as per NCCN guidelines (n =33/72% with ≤1 risk factor). All completed treatment successfully and achieved a complete remission (CR). One patient had minimal residual uptake (MRU) on interim PET scan (mediastinum 3.9; mediastinal blood pool 1.6) and was subsequently negative on post-treatment PET scan. Two patients had a positive PET scan (one interim, one post-treatment), both of which were biopsy-proven sarcoid. Two patients relapsed at 7 and 24 months after negative interim and post-treatment imaging: one relapse was identified by a surveillance scan; the other was simultaneous with the resumption of B symptoms and the presence of increasing lymphadenopathy on a surveillance scan. Forty-five patients experienced a durable CR, of whom 21 (45%) had additional unscheduled imaging or work-up during surveillance to investigate symptoms (i.e. night sweats, lymphadenopathy, pain) or imaging signs of concern. Five patients underwent further PET scans to confirm CR (all negative); 3 patients were found to have thymic hyperplasia and one was diagnosed with sarcoid. No additional failures were detected. The 2 relapsed patients are currently in CR after ASCT. Excluding relapses, the total cost of CT follow-up for all patients was $181, 720 and, including PETs, $210, 064, The median cost of CT follow-up for each patient was $3, 850 (range: $1, 540-$7, 700) and the median cost of all follow-up (CT and PET) for each patient was $4, 620 (range: $2, 310-$8, 881).
Due to a low risk of relapse, post-treatment radiologic surveillance appears unnecessary in early-stage, nb cHL patients (as defined above) who achieve a PET-CR with 6 cycles of ABVD. Its elimination will also reduce cumulative radiation exposure and healthcare costs in a predominantly young patient population.
No relevant conflicts of interest to declare.
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