A multicentre study of primary breast diffuse large B-cell lymphoma in the rituximab era.

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.

A retrospective analysis of peripheral T-cell lymphoma treated with the intention to transplant in the first remission.

BACKGROUND: Peripheral T-cell lymphomas are aggressive lymphomas that have no standard treatment. Studies suggest that HD-ASCT in the first CR improves outcome. Few data exist regarding allo-HSCT in the first CR. PATIENTS AND METHODS: We retrospectively identified patients (2001-2011) with PTCL-not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, initially treated with CHOP, CHOP-ICE (ifosfamide, carboplatin, etoposide), or other therapy with the intention to transplant in the first CR. Disease characteristics, therapy, progression-free survival (PFS), and OS were evaluated. RESULTS: Sixty-five patients were identified. PFS and OS were 38% and 52%, respectively, at 4 years. CHOP and CHOP-ICE regimens had similar outcomes. Treatment with allo-HSCT and HD-ASCT had OS at 4 years of 66% and 67%, respectively. Patients who did not proceed to transplant had OS of 27%. IPI score ≤ 2 and Prognostic Index for T-cell Lymphomas scores ≤ 1 predicted improved outcome. Combined analysis of interim response to CHOP and IPI score also predicted PFS and OS. CONCLUSION: Our results support consolidation of first CR with transplantation. The addition of etoposide did not improve outcomes. Baseline IPI and interim response to CHOP can predict outcomes and guide decisions about transplantation in first CR in PTCL. Randomized trials are necessary to confirm the efficacy of this approach.

Intensive induction chemotherapy followed by early high-dose therapy and hematopoietic stem cell transplantation results in improved outcome for patients with hepatosplenic T-cell lymphoma: a single institution experience.

INTRODUCTION: Hepatosplenic T-cell lymphoma is a rare form of extranodal non-Hodgkin lymphoma, first recognized as a distinct entity in the Revised European-American Lymphoma classification. Typical presentation includes lymphomatous infiltration of spleen and liver, and peripheral lymphadenopathy is rarely seen. The prognosis is almost uniformly poor, and there are no prospective studies of treatment of HSTCL. PATIENTS AND METHODS: For this report, we conducted a retrospective review of all pts who underwent treatment for HSTCL at our institution. Individual chart review was performed to report clinical presentation, management, and outcome. RESULTS: We identified 14 pts with HSTCL managed at our center, 7 of which remain alive with median follow-up of 65.6 months. Six of 7 received alternative induction chemotherapy regimens such as ICE (ifosfamide, carboplatin, etoposide) or IVAC (ifosfamide, etoposide, high-dose cytarabine) as opposed to CHOP and all surviving pts had proceeded to undergo either autologous or allogeneic SCT. CONCLUSION: Our results suggest that use of non-CHOP induction regimen and early use of high dose therapy and SCT consolidation may translate to improved survival for pts with HSTCL.

ABVD alone and a PET scan complete remission negates the need for radiologic surveillance in early-stage, nonbulky Hodgkin lymphoma.

BACKGROUND: Patients with early-stage, nonbulky classic Hodgkin lymphoma (cHL) undergo intensive posttreatment radiologic surveillance despite having a low risk of disease recurrence. The current study attempted to evaluate the risk of disease recurrence and the value of radiologic surveillance in patients treated with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment positron emission tomography (PET). METHODS: Forty-seven patients who underwent therapy with interim and/or posttreatment PET scans were evaluated for disease recurrence during ≥ 24 months of follow-up. Their presenting characteristics and imaging results were assessed and interpreted in relation to clinical outcome. RESULTS: All 47 patients were eligible for analysis. The majority of patients were female (35 patients) with a median age of 28 years (range, 17 years-65 years.). The nodular sclerosing subtype was the predominant histology (41 patients). A total of 34 patients were staged with IIA disease, 6 with IA disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to Cotswolds modification of the Ann Arbor staging system). All patients completed 6 cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1 interim scan and 1 posttreatment scan); both were biopsy-proven sarcoidosis. Two patients developed disease recurrence at 7 months and 24 months, respectively, after negative interim and posttreatment imaging. One case of recurrence was identified through surveillance imaging and the other was identified simultaneously by the patient and surveillance scan. A total of 45 patients experienced a durable CR; 21 had additional unscheduled imaging/workup during surveillance to investigate symptoms or imaging signs of concern. CONCLUSIONS: Because of a low risk of disease recurrence, posttreatment radiologic surveillance appears to be unnecessary in patients with early-stage, nonbulky (CD20 negative) cHL who achieve a PET-detected CR with the ABVD combination alone. This will reduce cumulative radiation exposure and health care costs in a predominantly young patient population.

Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma.

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) (18)FDG-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.

Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres.

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.

Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma.

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.