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Purpose: The median survival for aggressive non-Hodgkin's lymphomas relapsing after or refractory to high-dose therapy and autologous stem cell transplantation therapy is 6.2 months. In these cases, there is limited salvageability with the use of conventional therapy. The purpose of this retrospective analysis was to evaluate single-agent rituximab as treatment for aggressive non-Hodgkin's lymphomas in these cases.Patients and Methods: Between January 1997 and February 2000, we treated 17 patients with aggressive non-Hodgkin's lymphomas whose disease was refractory to, or relapsed after, autologous stem cell transplantation. Treatment consisted of rituximab, 375 mg/m2 as a single agent for four weekly doses. Thirteen patients had diffuse large B-cell lymphoma, and four patients had mantle cell lymphoma. The median time from autologous stem cell transplantation to relapse was 10 months (range, 2-40 months). The median number of prior therapies, including autologous stem cell transplantation, was three (range, 2-6).Results: The overall response rate to rituximab was 53%, and there were four complete responses and five partial responses. Seven of 13 patients with diffuse large B-cell lymphoma (three complete responses, four partial responses) responded, and two of four patients with mantle cell lymphoma (one complete responses, one partial responses) responded. The median progression-free survival for all responders was 13 months (range, 6-18 months). Four responders (two complete responses, two partial responses) were re-treated with a second course of rituximab for disease recurrence and responded to further antibody therapy. Rituximab was well tolerated with no serious adverse events.Discussion: Rituximab is effective and well-tolerated palliative treatment for aggressive non-Hodgkin's lymphomas that relapse after or is refractory to autologous stem cell transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that patients with nongerminal center B-cell like (non-GCB) have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score-matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the patients with GCB (n = 69) and non-GCB (n = 69) at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR, 0.68; 95% CI, 0.33-1.42). Propensity score-matched patients from MSK (n = 108) demonstrated a small attenuation in the HRs for EFS (HR, 0.57; 95% CI, 0.27-1.18) and OS (HR, 0.76; 95% CI, 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n = 108) demonstrated an EFS association (HR, 1.17; 95% CI, 0.70-1.95) and OS association (HR, 1.13; 95% CI, 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population. This trial was registered at www.ClinicalTrials.gov as #NCT00039195 and #NCT00712582., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment., Patients and Methods: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay., Results: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse., Conclusion: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of lymphoma that, like other Hodgkin lymphomas, has historically been treated aggressively. However, in most cases, NLPHL has an indolent course, which raises the question of to what extent these patients require aggressive upfront treatment. We describe the management and outcomes of consecutive NLPHL patients diagnosed at Memorial Sloan Kettering Cancer Center (MSK), with a focus on evaluating active surveillance. All patients aged 16 years or older diagnosed and followed at MSK between 1974 and 2016 were included. Treatment outcomes were compared between management with active surveillance and other strategies. We identified 163 consecutive patients who were treated with radiotherapy alone (46%), active surveillance (23%), chemotherapy (16%), combined modality (12%), or rituximab monotherapy (4%). Median follow-up was 69 months. Five-year progression-free survival (PFS), second PFS (PFS2), and overall survival (OS) estimates were 85% (95% confidence interval [CI], 78-90), 97% (95% CI, 92-99), and 99% (95% CI, 95-100), respectively. Only 1 of 7 deaths was lymphoma related. Patients managed with active surveillance had slightly shorter PFS than those receiving any active treatment, with 5-year PFS of 77% (95% CI, 56-89) vs 87% (95% CI, 79-92; P = .017). This difference did not translate into better PFS2 or OS. Only 10 patients managed with active surveillance (27%) eventually required treatment, after a median of 61 months, and none died. NLPHL has an excellent prognosis. Within the limitations of a retrospective analysis, active surveillance is a viable initial management strategy for selected NLPHL patients., (© 2019 by The American Society of Hematology.)

In the postrituximab era, approximately half of the patients with relapsed or refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) fail to achieve a chemosensitive response to standard salvage therapy, and are thus ineligible to proceed to autologous stem cell transplantation with curative intent. The Bruton tyrosine kinase inhibitor ibrutinib demonstrates single-agent activity in rel/ref DLBCL, particularly of non-germinal center (non-GC) cell of origin. We conducted a single-center phase 1 study evaluating dose-escalated ibrutinib, in a 3-by-3 design, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in physiologically transplant-eligible rel/ref DLBCL patients. Twenty-one patients have been treated and are evaluable for toxicity with no dose-limiting toxicities observed through expansion with ibrutinib at 840 mg daily at dose level 3. Of the 20 patients evaluable for response, per modern International Conference on Malignant Lymphoma criteria, 11 patients achieved complete remission (CR) and 7 patients achieved partial remission for an overall response rate of 90%. All evaluable patients with non-GC DLBCL achieved a metabolic CR. Ibrutinib in combination with R-ICE demonstrates tolerability and efficacy in rel/ref DLBCL, particularly of non-GC phenotype. This treatment program warrants further investigation in later-phase studies. This trial was registered at www.clinicaltrials.gov as #NCT02219737., (© 2018 by The American Society of Hematology.)

Identification of prognostic factors for patients with relapsed/refractory Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase 2 study of positron emission tomography (PET)-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, and etoposide (augICE), we assessed clinical factors, quantitative PET assessments, and cytokine and chemokine values. Transplant-eligible patients with relapsed/refractory HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative patients (Deauville score ≤2) proceeded to autologous stem cell transplantation (ASCT) whereas PET-positive patients received augICE before ASCT. Serum cytokine and chemokine levels were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis were measured at baseline, after BV, and after augICE. Sixty-five patients enrolled (45, cohort 1; 20, cohort 2); 49 (75%) achieved complete response and 64 proceeded to ASCT. Three-year overall survival and event-free survival (EFS) were 95% and 82%, respectively. Factors predictive for EFS by multivariable analysis were baseline MTV (bMTV) ( P < .001) and refractory disease ( P = .003). Low bMTV (<109.5 cm 3 ) and relapsed disease identified a favorable group (3-year EFS, 100%). For patients who received a transplant, bMTV and pre-ASCT PET were independently prognostic; 3-year EFS for pre-ASCT PET-positive patients with low bMTV was 86%. In this phase 2 study of PET-adapted therapy with BV and augICE for relapsed/refractory HL, bMTV and refractory disease were independent prognostic factors for EFS. Furthermore, bMTV improved the predictive power of pre-ASCT PET. Future studies should optimize efficacy and tolerability of salvage therapy by stratifying patients according to risk factors such as bMTV., (© 2017 by The American Society of Hematology.)

Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20-400 mg twice a day, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m 2 intravenously, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the maximum tolerated dose (MTD) with rituximab (375 mg/m 2 , day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in seven dose-escalation cohorts and seven patients in the dose-expansion cohort. Results: The MTD was veliparib 300 mg twice daily plus bendamustine 90 mg/m 2 Dose-limiting toxicities (DLT) were anemia, nausea, hypertension, and hyperhidrosis. Grade ≥3 toxicities included lymphopenia (87.8%), anemia (19.5%), neutropenia (12.2%), thrombocytopenia (9.8%), leukopenia (9.8%), nausea (7.3%), and hypophosphatemia (7.3%). Apparent veliparib clearance was slightly lower than previously reported. Of 14 patients with lymphoma evaluable for response, five of seven (71%) on VB and six of seven (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response. Conclusions: VB and VBR were generally well-tolerated. VBR had preliminary clinical activity in patients with B-cell lymphoma, which warrants further investigation in a phase II trial. This trial was registered at www.clinicaltrials.gov as NCT01326702 Clin Cancer Res; 23(15); 4119-26. ©2017 AACR ., (©2017 American Association for Cancer Research.)

This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451., (© 2016 by The American Society of Hematology.)

Background: This study evaluated the need for surveillance imaging in early-stage classic Hodgkin lymphoma (cHL) after planned combined-modality therapy (CMT)., Methods: Primary early-stage cHL patients who underwent CMT were included. Positron emission tomography (PET)/computed tomography (CT), CT, or both were performed at the initial staging, during or after chemotherapy, and for at least 2 years during follow-up. Imaging studies and medical records were reviewed to determine if and when relapse had occurred. Radiation doses and costs were also calculated from follow-up imaging., Results: The study included 78 patients with a median follow-up of 46 months; 85% of the patients had stage II disease (32% with bulky disease). Four of 77 interim PET scans were positive; none of these patients relapsed during follow-up, which ranged from 24 to 80 months. After a total of 466 follow-up imaging studies (91% with CT and 9% with PET/CT), no cHL relapse was detected. Eleven abnormal findings were noted on surveillance imaging: 9 were false-positives, and 2 were second primary malignancies. The average cumulative dose per patient from follow-up imaging was 107 mSv, which translated into an estimated lifetime excess cancer risk of 0.5%; the estimated total costs were $296,817 according to Medicare reimbursements., Conclusions: Surveillance imaging with either CT or PET/CT can be omitted safely for early-stage cHL treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy because the risk of relapse is extremely low. This observation also applies to patients with bulky disease. The elimination of surveillance imaging will also reduce healthcare expenses and cumulative radiation doses in these predominantly young patients., (© 2015 American Cancer Society.)

Background: Pre-transplantation (18)F-fluorodeoxyglucose (FDG) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant (HDT/ASCT) for patients with relapsed or refractory Hodgkin's lymphoma. In this study, we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin, followed by augmented ifosfamide, carboplatin, and etoposide (ICE)., Methods: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients with relapsed or refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen. All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin on days 1, 8, and 15 for two 28 day cycles. After completion of brentuximab vedotin treatment, patients received a PET scan. Patients who achieved PET-negative status (a Deauville score of 1 or 2) proceeded directly to HDT/ASCT; those with persistent abnormalities on PET received two cycles of augmented ICE (augICE; two doses of ifosfamide 5000 mg/m(2) in combination with mesna 5000 mg/m(2) continuous infusion over 24 h, days 1 and 2; one dose of carboplatin AUC 5, day 3; three doses of etoposide 200 mg/m(2) every 12 h, day 1) before consideration for HDT/ASCT. Only patients with persistent abnormalities on PET after brentuximab vedotin received augICE; however, all patients in the intention-to-treat population were assessed for the primary outcome, which was the proportion of patients who were PET-negative after brentuximab vedotin alone or brentuximab vedotin followed by augICE. This study is registered with ClinicalTrials.gov, number NCT01508312, and is no longer accruing patients., Findings: Between Jan 5, 2012, and Oct 4, 2013, we enrolled 46 patients. One patient was deemed ineligible, and not evaluable, before treatment initiation owing to having nodular, lymphocyte-predominant Hodgkin's lymphoma and thus 45 patients received treatment. After brentuximab vedotin, 12 patients (27%, 95% CI 13-40) were PET-negative and proceeded to HDT/ASCT. 33 (73%, 95% CI 60-86) patients were PET-positive after brentuximab vedotin; one PET-positive patient withdrew consent, therefore 32 PET-positive patients received augICE, 22 (69%, 95% CI 53-85) of whom were PET-negative. Overall, 34 patients (76%, 95% CI 62-89) achieved PET-negativity. All 44 patients who completed treatment as per protocol proceeded to receive HDT/ASCT. Brentuximab vedotin was well tolerated and associated with few grade 3-4 adverse events including hyperglycaemia (two [4%] patients, grade 3), nausea (one [2%], grade 3), hypoglycaemia (one [2%], grade 3 and one [2%], grade 4), and hypocalcaemia (one [2%], grade 3 and one [2%], grade 4)., Interpretation: PET-adapted sequential salvage therapy with brentuximab vedotin followed by augICE resulted in a high proportion of patients with relapsed or refractory Hodgkin's lymphoma achieving PET-negativity, and therefore could optimise the chance of cure after HDT/ASCT., Funding: Seattle Genetics., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: We have prospectively studied a three month course of clarithromycin (substituted by Prevpac ® , lansoprazole/ amoxicillin/ clarithromycin, in the first two wks when stool H pylori+) for non-bulky, advanced stage indolent lymphoma. These patients are often candidates for expectant monitoring and it is during this period that a window of opportunity may exist to identify and treat associated infections., Methods: All previously untreated patients with a new diagnosis of indolent lymphoma (FL and non-FL) meeting GELF criteria were treated with 12 weeks of clarithromycin. There were 32 evaluable patients, 4 of whom had stool H pylori., Results: At one month post-antibiotic therapy, we have observed lymphoma responses in 7 of 32 patients (21.9%). Two additional patients had objective response during followup (28.1% overall response). The median treatment free survival for antibiotic responders is 69.9 months and for non-responders, 30.6 months (p = 0.019)., Conclusion: Three response patterns have been noted, perhaps suggestive of an immune-mediated response -- prompt PET negative; flair with delayed PET negative response; and gradual continuous improvement. This prospective study appears promising, may be a step toward developing a lymphoma prevention strategy by reducing "antigen drive," and deserves further clinical/biological study. http://clinicaltrials.gov/show/NCT00461084.

Chronic hepatitis C virus (HCV) infection has been implicated in the induction and maintenance of B-cell lymphomas. The strongest evidence for this derives from clinical observations of tumor regressions upon antiviral treatments. Here we used multiple methods to test the hypothesis that the expansion of HCV-specific B cells gives rise to lymphomas. We obtained lymphoma tissues from HCV-infected lymphoma patients, including some that later regressed upon antiviral treatments. We expressed the lymphoma B-cell receptors as soluble immunoglobulin Gs and membrane IgMs, and analyzed their reactivity with HCV proteins and with HCV virions. We confirmed previous reports that HCV-associated lymphomas use a restricted immunoglobulin variable region gene repertoire. However, we found no evidence for their binding to the HCV antigens. We conclude that most lymphomas of HCV-infected patients do not arise from B cells aimed at eliminating the virus.

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., (Copyright © 2012 American Cancer Society.)

Purpose: Limited data exist regarding the activity of bendamustine in Hodgkin lymphoma (HL). This phase II study evaluated the efficacy of bendamustine in relapsed and refractory HL., Patients and Methods: Patients with relapsed and refractory HL who were ineligible for autologous stem-cell transplantation (ASCT), or for whom this treatment failed, received bendamustine 120 mg/m(2) as a 30-minute infusion on days 1 and 2 every 28 days with growth factor support. The primary end point was overall response rate (ORR). A secondary end point was referral rate to allogeneic stem-cell transplantation (alloSCT) for patients deemed eligible for alloSCT at the time of enrollment., Results: Of the 36 patients enrolled, 34 were evaluable for response. Patients had received a median of four prior treatments, and 75% had relapsed after ASCT. The ORR by intent-to-treat analysis was 53%, including 12 complete responses (33%) and seven partial responses (19%). The response rate among evaluable patients was 56%. Responses were seen in patients with prior refractory disease, prior ASCT, and prior alloSCT; however, no responses were seen in patients who relapsed within 3 months of ASCT. The median response duration was 5 months. Five patients (20% of those eligible) proceeded to alloSCT after treatment with bendamustine. Grade ≥ 3 adverse events were infrequent and most commonly included thrombocytopenia (20%), anemia (14%), and infection (14%)., Conclusion: This study confirms the efficacy of bendamustine in heavily pretreated patients with HL. These results support current and future studies evaluating bendamustine combinations in relapsed and refractory HL.

Hepatitis C virus (HCV) is a commonly transmitted infection that has both hepatic and extrahepatic repercussions. These range from the inflammatory to the oncologic with an undisputed link to hepatitis, liver cirrhosis, and hepatocellular carcinoma. Its role in the development of B cell non-Hodgkin lymphoma (B-NHL) is becoming better understood, leading to opportunities for research, therapy, and even prevention. Research in the field has progressed significantly over the last decade, with the number of patients diagnosed with HCV and B-NHL rising incrementally. It is therefore becoming crucial to fully understand the pathobiologic link of HCV in B cell lymphomagenesis and its optimal management in the oncologic setting., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Cardiac complications resulting from chemotherapy and radiation pose a significant risk for morbidity and mortality to the cancer survivor. Cardiac side effects may progress over time and are a concern for patients treated during childhood. Long-term pulmonary complications are relatively infrequent, and acute respiratory effects of drugs (mostly bleomycin) or radiation normally resolve early after therapy. Although most cardiovascular risk statistics and clinical experience are derived from patients treated before 1985, the modern radiation approach that limits the exposure of the heart and reduces the total dose seems to attenuate the previously observed cardiovascular risk. Potential preventive measures for high-risk patients are of increasing interest but remain experimental., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Respiratory signs and symptoms are commonly encountered by physicians who care for cancer patients. Supplemental oxygen (SOx) has long been used for treatment of hypoxic respiratory insufficiency, but data reveal mixed efficacy results. The use and outcome patterns of technologically advanced oxygen delivery devices, such as humidified high-flow nasal oxygen (HHFNOx), are incompletely understood., Methods: Institutional database search of the number of patient cases in which the current HHFNOx device was used, and abstraction of 183 patient medical records for usage characteristics., Results: Patients have been treated with HHFNOx at Memorial Sloan Kettering Cancer Center (MSKCC) since 2008. Of the 183 patients randomly selected for our study, 72% received HHFNOx in the intensive care unit (ICU) because of hypoxia. Patients usually improved (41%) or remained stable (44%) while on the device, whereas 15% declined. At study completion, 45% of patients were living, and 55% had died. The median time on HHFNOx was 3 days (range: 1-27). A do not resuscitate (DNR) order was present in 101 (55%) patients, either before (12%) or after (43%) device utilization. The majority (78%) of these 101 patients died at MSKCC., Conclusion: Dyspnea is a common and important symptom in cancer patients for which SOx traditionally has had no clear basis except in select cases of hypoxia and patient preference. Our institutional experience with HHFNOx contributes to the understanding of the applications and challenges surrounding the use of new medical devices in the cancer population. Physiologic and quality-of-life benefits of HHFNOx compared with traditional oxygen delivery methods should be studied prospectively.

PURPOSE In studies of diffuse large B-cell lymphoma, positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. PATIENTS AND METHODS From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. RESULTS At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.

Background: The Stanford group has reported excellent results with the Stanford V regimen for patients with bulky and/or advanced Hodgkin lymphoma (HL). However, Gobbi reported markedly inferior failure-free survival (FFS) comparing Stanford V to other regimens but included major deviations from the original program. We retrospectively examined whether treatment at our institution carefully following Stanford V guidelines would confirm the original Stanford outcome data., Patients and Methods: From June 1995 to May 2002, 126 patients with either locally extensive or advanced HL were treated with the 12-week Stanford V chemotherapy program followed by 36-Gy involved-field radiotherapy to sites initially > or =5 cm and/or to macroscopic splenic disease. Overall, 26% had stage IV disease and 20% had international prognostic score (IPS) > or =4. Overall survival (OS), disease-specific survival, progression-free survival (PFS), FFS, and freedom from second relapse (FF2R) were determined., Results: The 5- and 7-year OS were 90% and 88%, respectively. The 5-year FFS was 78%. IPS > or =4 was a significant independent predictor of worse OS and PFS. The FF2R was 64% at 3 years., Conclusion: Stanford V with appropriate radiotherapy is a highly effective regimen for locally extensive and advanced HL.

Background: The proliferative index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability. The mantle cell international prognostic index (MIPI) has been reported to have prognostic importance. In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL., Patients and Methods: Eighty-eight patients with adequate tissue were included in this analysis. Patients were treated with one of two treatment programs: sequential therapy with high-dose therapy consolidation or radioimmunotherapy followed by combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone. Patients were divided into four groups based on PI (<10%, 10%-29.9%, 30%-49.9%, and >50%), and outcomes were analyzed., Results: Thirty percent was identified as the optimal cut-off for PI. By univariate analysis, intensive treatment and a low PI were associated with a superior progression-free survival (PFS); only PI was associated with overall survival. By multivariate analysis, both intensive treatment and PI correlated with PFS. The MIPI had no prognostic impact., Conclusions: PI is the most important prognostic factor in MCL. The cut-off of 30% is clinically meaningful and can be used to tailor the intensity of therapy in future clinical trials.

Pertussis is a highly contagious respiratory infection characterized by prolonged cough and inspiratory whoop. Despite widespread vaccination of children aged<7 years, its incidence is steadily increasing in adolescents and adults, because of the known decrease in immunity following childhood immunization. In an effort to reduce pertussis in adolescents and adults, 2 vaccines containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) (BOOSTRIX and Adacel) were licensed in 2005 for use in adolescents, 1 of which (Adacel) contains less pertussis toxoid (PT) for use in adults. This study assessed pertussis titers in 57 adult survivors of an autologous peripheral blood stem cell transplantation (PBSCT; median age, 37.5 years), 28 of whom were subsequently vaccinated with Tdap containing 2.5microg of PT (Adacel). The median time to Tdap administration was 3 years posttransplantation. Before vaccination, 87% of the patients lacked pertussis immunity. Only 2 of the 28 patients developed a >2-fold response to PT following vaccination with Tdap. These data suggest that autologous transplantation recipients are highly susceptible to pertussis and that immunization with 2.5microg of PT induces an inadequate response. Prospective trials evaluating BOOSTRIX, containing 8microg/dose of PT (approved for adults in December 2008) are warranted in this vulnerable population undergoing transplantation.

Cardiac complications resulting from chemotherapy and radiation pose a significant risk for morbidity and mortality to the cancer survivor. Cardiac side effects may progress over time and are a concern for patients treated during childhood. Long-term pulmonary complications are relatively infrequent, and acute respiratory effects of drugs (mostly bleomycin) or radiation normally resolve early after therapy. Although most cardiovascular risk statistics and clinical experience are derived from patients treated before 1985, the modern radiation approach that limits the exposure of the heart and reduces the total dose seems to attenuate the previously observed cardiovascular risk. Potential preventive measures for high-risk patients are of increasing interest but remain experimental.

Background: Eradication of Helicobacter pylori in gastric mucosa-associated lymphoid tumor can result in lymphoma remission. We prospectively identified/treated infections in nonbulky, advanced stage indolent lymphoma (follicular; nonfollicular lymphoma) eligible for observation., Materials and Methods: Stool H. pylori, hepatitis C and Borrelia serologies, Borrelia and Chlamydia fixed tissue PCR, Chlamydia peripheral blood mononuclear cell PCR and hydrogen breath test for small bowel bacterial overgrowth (SBBO) were obtained., Results: Fifty-six patients were enrolled. Positive infections: H. pylori (13); hepatitis C (3); SBBO (11). Negative: Borrelia (13); Chlamydophila psittaci (12, except one PCR). Lymphoma responses to antimicrobial therapy: H. pylori [one complete response (CR), 24+ months; one transient near CR]; hepatitis C [two CRs, 18+ and 30+ months; one partial response (PR) but hepatitis C virus persistent]; SBBO (one PR, 30+ months). Patients with associated infections, but without lymphoma CR, have required lymphoma treatment sooner than those without initial infections (treatment-free survival at 23.4 months median follow-up, 40.5% versus 74.7%, P = 0.01), indicating a different biology., Conclusion: Infections are common in advanced stage indolent lymphoma (37.5% in our series). Anecdotal lymphoma responses have been seen and three have been durable CRs (18 to 30+ months) with infection eradication alone. The identification and treatment of associated infections may be a first step towards developing a lymphoma prevention strategy.

Introduction: HDT/ASCT is standard for relapsed and refractory DLCL patients responding to second-line chemotherapy. We incorporated a thrombopoietic agent into the ICE chemotherapy program to potentially: decrease platelet associated toxicities, augment stem cell collection and maintain dose intensity., Methods: This randomized, double-blind, placebo-controlled phase I/II trial examines PEG-rHuMGDF versus placebo with ICE chemotherapy. Phase I compared three cohorts and defined a clinically effective dose (CED). Phase II evaluated the CED versus placebo. Outcome measures included safety, hematological end-points, stem cell collection and the impact of dose-intensity on outcome., Results: Forty-one patients with primary refractory (16) or relapsed DLCL (25) were treated; Response rates for evaluable patients are: 75% (12/16) for placebo and 82% (18/22) for PEG-rHuMGDF. PEG-rHuMGDF treated patients had significantly less grade IV thrombocytopenia, higher median platelet nadirs, and less platelet transfusion per cycle. ICE dose intensity was improved with PEG-rHuMGDF versus placebo: 75 versus 42% (P = 0.008). At 8.5 years median follow-up, overall and event-free survival are 47 and 31%, respectively. Patients treated on PEG-rHuMGDF versus placebo had improved survival (59 versus 31%, P = 0.06)., Conclusion: PEG-rHuMGDF ameliorated thrombocytopenia, improved platelet recovery, and maintained ICE dose intensity. Potential survival advantages conferred by maintaining dose intensity require validation with newer thrombopoietic agents.

The anti-CD20 monoclonal antibody, rituximab, and interferon alpha (IFN) are active agents in advanced stage, indolent lymphoma. Some data obtained in vitro suggest upregulation of CD20 by IFN, and clinical trials have reported additive or synergistic activity of IFN with rituximab. A prospective phase II study in advanced stage, follicular and non-follicular indolent lymphoma was performed. Peginterferon alpha 2b (pegIFN) 0.5 microg/kg s.c. weekly x 6 and rituximab 375 mg/m2 i.v. weekly x 4 (beginning on week 3 of pegIFN) was administered. Quantitative CD20 antigen was measured pre-treatment and pre-rituximab in lymph node aspirates. Nine patients were treated: one complete response and three partial responses; however, all relapsed within 12 months and two were withdrawn for grade 3 toxicity (both with serum sickness). No up-regulation of CD20 was documented in seven patients studied (median change in CD20: decrease by 11.9%). PegIFN plus rituximab as delivered in this study is not recommended. PegIFN does not appear to upregulate CD20 expression in peripheral lymph node tumor cells.

Primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathological entity with unclear prognostic factors and optimal treatment approach. To elucidate an optimal treatment and identify predictive factors, a retrospective analysis of 141 consecutive patients was undertaken. Patients received cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone (CHOP)-like therapy, the non-Hodgkin lymphoma (NHL)-15 regimen or upfront autologous stem cell transplantation (ASCT) on Institutional Review Board approved trials or according to the institutional guidelines. Evaluation included lactate dehydrogenase, International Prognostic Index (IPI) assessment, computed tomography scan and gallium imaging. With a median follow-up of 10.9 years, event-free survival (EFS) and overall survival (OS) was 50% and 66% respectively. EFS/OS for CHOP/CHOP-like, NHL-15 and upfront ASCT was 34/51%, 60/84% and 60/78% respectively. CHOP/CHOP-like regimens had inferior EFS and OS versus NHL-15 or upfront ASCT (P < 0.001). A total of 23% of patients received radiotherapy. Multivariate analysis revealed the following outcome predictors: for EFS, greater than or equal to two extranodal sites and initial therapy received (NHL-15 or upfront ASCT); for OS, only initial therapy with NHL-15. We conclude: (i) dose-dense chemotherapy with NHL-15 may be superior to CHOP for PMLBL; (ii) The impact of consolidative radiotherapy requires randomised controlled trials; (iii) The age-adjusted IPI did not predict survival in this analysis; (iv) high-dose chemotherapy/ASCT should be reserved for upfront anthracycline-based therapy failure or in clinical trials for high-risk patients.

To determine whether combined modality therapy (CMT) is superior to chemotherapy (CT) alone, 152 untreated Hodgkin disease patients with clinical stages (CSs) IA, IB, IIA, IIB, and IIIA without bulk disease were prospectively randomized to 6 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone or 6 cycles of ABVD followed by radiation therapy (RT) (3600 cGy: involved field for 11 patients, modified extended field for the rest). Of 76 patients randomized to receive RT, 65 actually received it, and 11 did not (4 progressed, 1 had bleomycin toxicity, 6 refused). For ABVD + RT, the complete remission (CR) percentage was 94% and no major response, 6%. For ABVD alone, 94% achieved a CR; 1.5%, a partial response (PR); and 4.5%, no major response. At 60 months CR duration, freedom from progression (FFP), and overall survival (OS) for ABVD + RT versus ABVD alone are 91% versus 87% (P = .61), 86% versus 81% (P = .61), and 97% versus 90% (P = .08), respectively (log-rank). The 95% confidence intervals for CR duration, FFP, and OS differences at 5 years were -8% to 15%, -8% to 18%, and -4% to 12%, respectively. Although significant differences were not seen, it is possible that a benefit in outcome of less than 20% for CMT might be seen in a larger trial.

Background: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas., Patients and Methods: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/kg subcutaneous on days 3-10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II-IV, were eligible., Results: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5-141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%-15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients < or =60 years of age., Conclusions: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%-15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.

Objective: This article reviews the pathogenesis, diagnosis, and treatment of patients with primary gastric lymphoma, with special attention to the changing role of surgery., Summary Background Data: Primary gastric lymphomas are non-Hodgkin lymphomas that originate in the stomach and are divided into low-grade (or indolent) and high-grade (or aggressive) types. Low-grade lesions nearly always arise from mucosa-associated lymphoid tissue (MALT) secondary to chronic Helicobacter pylori (H. pylori) infection and disseminate slowly. High-grade lesions may arise from a low grade-MALT component or arise de novo and can spread to lymph nodes, adjacent organs and tissues, or distant sites., Methods: A review of the relevant English-language articles was performed on the basis of a MEDLINE search from January 1984 to August 2003., Results: About 40% of gastric lymphomas are low-grade, and nearly all these low-grade lesions are classified as MALT lymphomas. For low-grade MALT lymphomas confined to the gastric wall and without certain negative prognostic factors, H. pylori eradication is highly successful in causing lymphoma regression. More advanced low-grade lymphomas or those that do not regress with antibiotic therapy can be treated with combinations of H. pylori eradication, radiation therapy, and chemotherapy. Nearly 60% of gastric lymphomas are high-grade lesions with or without a low-grade MALT component. These lymphomas can be treated with chemotherapy and radiation therapy according to the extent of disease. Surgery for gastric lymphoma is now often reserved for patients with localized, residual disease after nonsurgical therapy or for rare patients with complications., Conclusion: The treatment of gastric lymphoma continues to evolve, and surgical resection is now uncommonly a part of the initial management strategy.

The prognostic significance of CD20 positive classical Hodgkin's disease (cHD) is uncertain. All cHD cases referred to the Memorial Sloan-Kettering Cancer Center (MSKCC) were retrospectively identified (5/92-11/00); the samples were immunostained, and clinical data ascertained. Cases were re-reviewed without knowledge of clinical outcome. Univariate and multivariate analyses were performed 248 patients had cHD: 28 CD20(+) (11%); 220 CD20(-). All clinical characteristics were comparable except haemoglobin level at presentation. With a median follow-up of 29.2 months, significant prognostic factors in multivariate analysis were: CD20 positivity, elevated white blood cell count (WBC) and low absolute lymphocyte count for time-to treatment failure (TTF); and for overall survival (OS), CD20 positivity, elevated WBC count, bone marrow involvement and age >/=45 years. TTF was significantly poorer for ABVD-treated patients with CD20(+) cHD as compared with CD20(-) cHD. Among 167 patients treated at MSKCC, both TTF (P < 0.0001) and OS (P = 0.017) were significantly decreased in CD20(+) patients as compared with CD20(-) cHD. CD20(+) cHD is a poor prognostic factor for TTF and OS. All cHD cases should be immunophenotyped for CD20. A large prospective trial is needed to confirm these findings.