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Craig H Moskowitz

Publications and source records attributed to Craig H Moskowitz.

11 recordsLinked to original sources
PubMed2006

Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma.

Autologous transplantation (ASCT) is the standard of care for chemosensitive relapsed or primary refractory aggressive lymphoma, but little is known about its efficacy in the subset of patients with peripheral T-cell lymphoma (PTCL). We undertook a retrospective review of patients with PTCL who underwent ASCT for relapsed or refractory disease after responding to second-line therapy, excluding patients with indolent histologies and those with anaplastic lymphoma kinase (ALK) expressing anaplastic large cell lymphoma. The results of 24 patients with PTCL were compared with those of 86 consecutive patients with chemosensitive relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL). With a median follow-up time of 6 years for surviving patients with PTCL and DLBCL, the 5-year progression-free survival (PFS) rates for PTCL and DLBCL patients were 24% and 34% respectively (P = 0.14); the corresponding overall survival (OS) rates were 33% and 39% respectively. There were no significant differences between the two groups with respect to time to disease progression or survival after progression. The second-line age-adjusted international prognostic index was the only variable prognostic for PFS and OS in a multivariate analysis. The outcome of ASCT for patients with chemosensitive relapsed or primary refractory PTCL is similar to that for patients with DLBCL.

Adolescent↗
PubMed2005

Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL.

A number of prognostic factors affect outcome in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory disease and the second-line age-adjusted international prognostic index. In de novo DLBCL, the cell of orgin, as determined by expression microarray analysis or immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the cell of origin, as well as other pathologic markers of outcome, on the repeat biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide, carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they prognostic in the salvage setting. Pretreatment clinical factors were well balanced between the cohorts. There was no significant difference in response to SLT, HDT, event-free or overall survival based on the cell of origin or any of the common pathologic markers examined. The cell of origin as determined by IHC does not predict outcome in transplantation-eligible patients with relapsed or primary refractory DLBCL.

Aged↗
PubMed2005

R-CHOP-14 in patients with diffuse large B-cell lymphoma: feasibility and preliminary efficacy.

Treatment of diffuse large B-cell lymphoma (DLBCL) with CHOP-21 (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg for 5 days every 21 days) results in long-term remission in approximately 45% of patients. Recent phase III trials have demonstrated improved survival by modifying CHOP either through adding rituximab or shortening the time between cycles to 14 days. These studies prompted our institution to treat newly diagnosed patients with DLBCL refusing or not eligible for protocol-based therapy with R-CHOP-14. In this single-institution retrospective analysis, we report our results with this regimen. Forty-nine patients with newly diagnosed DLBCL and ineligible or refusing protocol-based therapy were retrospectively identified. Patients were treated with 6-8 cycles of R-CHOP-14 given with filgrastim and prophylactic antibiotics. The main toxicities with R-CHOP-14 were hematological and neurological and were not unexpected. There were no treatment-related deaths. Patients received 90% of planned cytotoxic drug density. The complete remission/complete remission uncertain (CR/CRu) rate was 82.2%. At a median follow-up of 24 months, the event-free survival was 80% and overall survival 90%. These results demonstrate R-CHOP-14 can be given to patients safely and short-term results regarding survival are promising. Whether adding rituximab and increasing dose intensity improves survival over either alone will require randomized studies.

Antibodies, Monoclonal↗
PubMed2005

Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999.

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.

Adolescent↗
PubMed2004

Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma.

Patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) who achieve complete response (CR) before autologous stem cell transplantation (ASCT) generally have better outcomes than those who achieve only partial response (PR). We investigated whether adding rituximab to the ifosfamide-carboplatin-etoposide (ICE) chemotherapy regimen (RICE) could increase the CR rate of patients with DLBCL under consideration for ASCT. Thirty-six eligible patients were treated with RICE, and 34 received all 3 planned cycles. The CR rate was 53%, significantly better than the 27% CR rate (P =.01) achieved among 147 similar consecutive historical control patients with DLBCL treated with ICE; the PR rate was 25%. Febrile neutropenia was the most frequent grade 3 or 4 nonhematologic toxicity; it occurred in 7.5% of delivered cycles. No patient had RICE-related toxicity that precluded ASCT. The median number of CD34(+) cells per kilogram mobilized was 6.3 x 10(6). Progression-free survival rates of patients who underwent transplantation after RICE were marginally better than those of 95 consecutive historical control patients who underwent transplantation after ICE (54% vs 43% at 2 years; P =.25). RICE appears to induce very high CR rates in patients with relapsed and refractory DLBCL; however, further studies are necessary to determine whether this treatment regimen will improve outcomes after ASCT.

Adolescent↗
PubMed2004

Differential expression patterns of c-REL protein in classic and nodular lymphocyte predominant Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) is characterized by numerical gains of the short arm of chromosome 2. The high frequency of 2p overrepresentation including REL, particularly in the nodular sclerosis subtype suggests that constitutive activation of nuclear factor kappaB/REL is a hallmark of Reed-Sternberg (RS) cells. The aim of this study was to investigate c-Rel protein expression patterns in cHL and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) cases by immunohistochemical analysis. A total of 79 cases of HL were analyzed, which included 59 cases of cHL (49 nodular sclerosis; 8 mixed cellularity; 2 lymphocyte-rich) and 20 cases of NLPHL. Positive staining was defined in this study as a reaction seen in the nuclei or nuclei and cytoplasm of RS or lymphocytic and histiocytic (L&H) cells in cHL and NLPHL cases, respectively. The percent positivity of c-REL staining of RS cells in cHL was seen in 51 of 59 cases (86.4%). No significant difference in c-REL expression was seen between nodular sclerosis (42 of 49, 85.7%) and mixed cellularity subtypes (7 of 8 cases, 87.5%; P = 1). In comparison, positive c-REL protein expression in L&H cells was seen in 5 of 20 NLPHL cases (25.0%). Therefore, significantly higher positivity of RS cells in cHL was seen compared with positivity of L&H cells in NLPHL; 86.4% vs. 25.0%; P = 0). Expression of Epstein-Barr virus latent membrane protein was seen in 6 of 30 cases (19.0%; 25 cHL, 5 NLPHL) and EBER1 in 5 of 27 cases (18.5%; 24 cHL, 3 NLPHL). The presence of Epstein-Barr virus did not correlate with c-REL protein expression (P = 1). Our results demonstrate that there is differential c-REL protein expression in cHL in comparison with NLPHL and suggest that c-REL may play a role in the pathogenesis of classic Hodgkin lymphoma.

Adolescent↗
PubMed2004

Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease.

Prospective randomized studies have determined that high dose therapy and autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed Hodgkin's disease (HD); however, the role of this approach in patients with primary refractory disease has been controversial. This report is an integrated analysis of 75 consecutive patients with biopsy-confirmed primary refractory HD, who were treated with high dose chemoradiotherapy (HDT) and ASCT at the Memorial Sloan Kettering Cancer Center. The patients underwent conventional dose cytoreductive chemotherapy followed by HDT and ASCT. At a median follow-up of 10 years for surviving patients, the event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) rates were 45%, 49% and 48% respectively. Only chemosensitivity to standard-dose second-line chemotherapy (SDSC) predicted for a better survival, thus responding patients had an EFS, PFS and OS of 60%, 62% and 66%, respectively, versus 19%, 23% and 17% for patients who had a poor response to SDSC (P < 0.001). While patients with chemosensitive disease have an excellent outcome with HDT and ASCT, novel approaches are needed to cure HD patients who fail front-line and second-line chemotherapy.

Adolescent↗
PubMed2003

Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis.

PURPOSE: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue. RESULTS: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity. CONCLUSION: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.

Adult↗
PubMed2003

Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma.

Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P <.001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P <.001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens.

Adolescent↗
PubMedDate not supplied

Rituximab for aggressive non-Hodgkin's lymphomas relapsing after or refractory to autologous stem cell transplantation.

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.

Adult↗