Role of a Doxorubicin-Containing Regimen in Relapsed and Resistant Lymphomas: An 8-Year Follow-Up Study of EPOCH

2000 ◽  
Vol 18 (21) ◽  
pp. 3633-3642 ◽  
Author(s):  
Martin Gutierrez ◽  
Bruce A. Chabner ◽  
Debra Pearson ◽  
Seth M. Steinberg ◽  
Elaine S. Jaffe ◽  
...  
Keyword(s):  
De Novo ◽  
International Prognostic Index ◽  
Oral Prednisone ◽  
Prognostic Index ◽  
Resistant Disease ◽  
Highly Effective ◽  
Clinically Significant ◽  
Hodgkin's Lymphomas

PURPOSE: Curative up-front regimens for non-Hodgkin’s lymphomas contain doxorubicin, vincristine, and cyclophosphamide, whereas salvage regimens generally contain non–cross-resistant agents. We hypothesized that up-front agents may be highly effective for salvage and developed an infusional regimen based on in vitro evidence of increased efficacy. PATIENTS AND METHODS: A prospective phase II study of etoposide, vincristine, and doxorubicin over 96 hours with bolus cyclophosphamide and oral prednisone (EPOCH) was performed in 131 patients with relapsed or resistant lymphoma. RESULTS: Seventy-nine percent of patients had aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% had resistant disease. Eighty-eight percent of patients had received at least four of the agents in EPOCH, and 94% had received doxorubicin. In 125 assessable patients, 29 (24%) achieved complete responses and 60 (50%) achieved partial responses. Among 42 patients with resistant disease, 57% responded, and in 28 patients with relapsed aggressive de novo lymphomas, 89% responded with 54% complete responses. With a median follow-up of 76 months, the overall and event-free survivals (EFS) were 17.5 and 7 months, respectively. In 33 patients with sensitive aggressive disease who did not receive stem-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily hematologic, with an 18% incidence of febrile neutropenia. No clinically significant cardiac toxicity was observed, despite no maximum cumulative doxorubicin dose. CONCLUSION: EPOCH is highly effective in patients who had previously received most/all of the same drugs and produces durable remissions in curable subtypes. Salvage regimens need not contain non–cross-resistant agents, and infusional schedules may partially reverse drug resistance and reduce toxicity.

L-mind: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large b-cell lymphoma (R-R DLBCL)—A single-arm phase II study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7514-7514 ◽  
Author(s):  
Kami J. Maddocks ◽  
Eva González Barca ◽  
Wojciech Jurczak ◽  
Anna Marina Liberati ◽  
Johannes Duell ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
International Prognostic Index ◽  
Single Agent ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Transplant ◽  
Cell Of Origin

7514 Background: The Fc-enhanced CD19 antibody MOR208 and the immunomodulatory drug LEN have demonstrated single agent activity in patients (pts) with R-R DLBCL. MOR208 and LEN have shown synergy in vitro and in vivo in preclinical lymphoma models. This ongoing phase II study assesses the safety and efficacy of MOR208 + LEN in pts with R-R DLBCL. Methods: Pts >18 years old with R-R DLBCL, ECOG 0–2, adequate organ function, having previously received ≥1 but not more than 3 prior therapies, including ≥1 CD20-targeting regimen and who are not candidates for autologous stem cell transplant (ASCT), are eligible. Treatment comprises up to 12, 28-day (d) cycles (C) of MOR208 12 mg/kg IV, weekly during C1–3 (loading dose d4 of C1); every second week C4–12 + LEN 25 mg po d1–21, C1–12. Pts progression-free after 12 cycles receive up to 12 additional cycles of MOR208 (every second week). The primary endpoint is the overall response rate (ORR) by central radiology assessment. Secondary endpoints include disease control, duration of response, progression-free and overall survival, safety, and response by cell of origin and other biomarkers. A preplanned safety evaluation was undertaken. Results: 31 of 80 planned pts were enrolled prior to data cutoff (3 January 2017). Median age was 74 years (range 47–82); 45% of pts received ≥2 prior lines of therapy; 23% had rituximab refractory disease; 74% had Ann Arbor stage ≥III disease; 65% had elevated lactate dehydrogenase level, and 52% had a poor revised International Prognostic Index (3-5). The most common treatment-emergent adverse events (any grade/grade ≥3 [% pts]) were neutropenia (39/26), anemia (23/0) thrombocytopenia (16/6), infections (26/10) diarrhea (13/0), pyrexia (13/0), and rashes (13/6). Of 26 response evaluable pts (median follow-up 3.3 months), ORR (investigator assessed) was 58% (15 pts), with 7 (27%) complete responses. Median time to response was 1.8 months. Conclusions: The combination of MOR208 + LEN is well tolerated and shows promising activity in pts with R-R DLBCL. Accrual and follow-up of pts is ongoing, as are cell of origin and other biomarker analyses. Clinical trial information: NCT02399085.

Long-Term Follow-up of Rituximab and Infusional Cyclophosphamide, Doxorubicin, and Etoposide (CDE) In Combination with HAART In HIV-Related Non-Hodgkin's Lymphomas (NHL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5072-5072
Author(s):  
Michele Spina ◽  
Ulrich Jaeger ◽  
Joseph A Sparano ◽  
Renato Talamini ◽  
Giuseppe Rossi ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
High Grade ◽  
Long Term Follow Up ◽  
Hodgkin's Lymphomas

Abstract Abstract 5072 Background: The combination of Rituximab plus chemotherapy (CT) is more effective than CT alone in the treatment of high grade NHL. Objective: To report the long-term follow-up of CDE plus Rituximab in HIV-NHL. Methods: In June 1998, we started a phase II study using infusional CDE (Cyclophosphamide 187.5 mg/m2/day, Doxorubicin 12.5 mg/m2/day and Etoposide 60 mg/m2/day) administered by continuous intravenous infusion for 4 days every 4 weeks and Rituximab 375 mg/m2 i.v. on day 1. HAART was given concomitantly with CT. Results: Seventy-four patients (pts) have been enrolled. The median CD4+ cell count was 161 (range 3–691) and the median Performance Status was 1 (range 0–3). Diffuse large B-cell NHL was diagnosed in 72% of pts and Burkitt in 28%. Seventy per cent of pts had advanced stage (III-IV) disease and 57% of pts had an age-adjusted international prognostic index >2. Fifty-two out of 74 pts (70%) achieved a complete remission (CR), 4/74 (5%) had a partial remission and 18 pts progressed. With a median follow-up of 61 months, only 17% of CRs have relapsed and 41/74 pts are alive. The overall survival, disease free survival and time to treatment failure (TTF) at 5 years were 56%, 81% and 52%, respectively. Four cases of secondary tumors have been observed. No case of late pulmonary or cardiac toxicity has been reported. Conclusions: The combination of Rituximab and CDE in HIV-NHL treated concomitantly with HAART is very active. CR rate (70%) and TTF at 5 years (52%) are comparable to those observed in high grade NHL of the general population. Our data confirm that in HAART era a high proportion of HIV-NHL can be cured. Disclosures: No relevant conflicts of interest to declare.

Safety and Efficacy of High-Dose Cyclophosphamide, Etoposide, and Ranimustine (CEM) Regimen Followed by Autologous Peripheral Blood Stem Cell Transplantation for Patients with High Risk De Novo Diffuse Large B-Cell Lymphoma or Diffuse Large B-Cell Lymphoma Associated with Follicular Lymphoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3121-3121
Author(s):  
Yujin Kobayashi ◽  
Yoshihiro Hatta ◽  
Atsuko Hojo ◽  
Masaru Nakagawa ◽  
Machiko Kusuda ◽  
...  
Keyword(s):  
High Risk ◽  
De Novo ◽  
Late Onset ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
History Of ◽  
Autologous Pbsct

Abstract Abstract 3121 Background We evaluated the safety and efficacy of the CEM regimen containing ranimustine (MCNU) with autologous peripheral blood stem cell transplantation (PBSCT) in adult patients with relapsed or high-risk de novo DLBCL or DLBCL associated with follicular lymphoma (FL/DLBCL) in our institution. Patients and methods We retrospectively analyzed 55 consecutive patients who underwent autologous PBSCT following the CEM regimen between March 1999 and June 2011 for the treatment of relapsed or high-risk DLBCL and FL/DLBCL. High-risk DLBCL was defined as partial or no response to initial treatment or high-intermediate/high risk disease according to international prognostic index (IPI) at initial diagnosis. Age-adjusted IPI was used for patients under 60. The CEM regimen consisted of CY (60 mg/kg on days -7 and -6), etoposide (500 mg/m2 on days -6 to -4) and MCNU (250 mg/m2on day -3 and -2), followed by PBSCT. Results Median age at transplant was 51 years (range, 23–66), and median time from diagnosis to transplant was 5 months (range, 3–241). Of them, 7 patients received radiation therapy before transplant, and 11 had no history of rituximab use before transplant. The 36 patients in CR1 at transplant were with high or high-intermediate risk according to international prognostic index at diagnosis. Other 15 patients in CR2, and 4 patients who were not in CR1/2 at transplant were included. CY dose was reduced in five patients by physicians choice. The median number of infused CD34-positive cells was 3.98 × 106/kg (range, 1.36–26.87). The median post-transplant days of neutrophil recovery and platelet were 11 days (range, 9–20) and 12 days (range, 7–53), respectively. Common grade 3/4 non-hematological treatment-related toxicities within the first 100 days after transplant were nausea (24%), vomit (4%), stomatitis (15%), and diarrhea (9%). Infections included febrile neutropenia (85%), sepsis (15%) which contained catheter-related bacteremia (n=4) and pneumonia (n=2). Other less common severe toxicities were acute renal impairment (n=3), and pleural effusion (n=1). No sever cardiac, neurologic toxicity, or veno-occlusive disease of the liver was observed in any of the patients. Late-onset adverse effects during follow-up period includes chronic renal impairment (n= 5), therapy-related myelodysplastic syndrome (refractory anemia) (n=1, 120 months), and prostate cancer (n=1, 83 months). Serious late cardiac or pulmonary impairment was not diagnosed in this cohort. Median follow-up duration of 42 patients surviving at the time of the analysis was 52 months (range, 1–159). Relapse or disease progression after PBSCT was documented in 21 cases (range, 0–81 months after PBSCT). No therapy related mortality (TRM) associated with PBSCT was observed, and all the 13 deaths were due to disease relapse/progression. The 5-year estimated overall survival (OS) and progression-free survival (PFS) were 70.6% (95% CI, 54.0–82.1)% and 57.0% (95% CI, 39.5–71.2)% for all patients, respectively. In a univariate analysis for factors affecting OS and PFS, no significant factors associated with unfavorable OS and PFS was found including age at transplant, gender, history of rituximab use, histology, disease status at transplant, and previous BM involvement. Conclusion We conclude that the CEM regimen using MCNU would be a tolerable, effective conditioning regimen of autologous PBSCT for high-risk or relapsed de novo DLBCL or FL/DLBCL. Although no TRM was observed, relapse was the major cause of treatment failure. Late-onset complications in long-term survivors can occur, and should be carefully monitored. Disclosures: No relevant conflicts of interest to declare.

Long-Term Follow-up of Rituximab and Infusional Cyclophosphamide, Doxorubicin, and Etoposide (cde) in Combination with HAART in HIVRelated Non-Hodgkin’s Lymphomas (NHL).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1467-1467
Author(s):  
Michele Spina ◽  
Cecilia Simonelli ◽  
Emanuela Vaccher ◽  
Ulrich Jaeger ◽  
Joseph Sparano ◽  
...  
Keyword(s):  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
High Grade ◽  
Cd4 Cell Count ◽  
Long Term Follow Up ◽  
Hodgkin's Lymphomas

Abstract Background: The combination of Rituximab plus chemotherapy (CT) is more effective than CT alone in the treatment of high grade NHL. Objective: To report the long-term follow-up of CDE plus Rituximab in HIV-NHL. Methods: In June 1998, we started a phase II study using infusional CDE (Cyclophosphamide 187.5 mg/m2/day, Doxorubicin 12.5 mg/m2/day and Etoposide 60 mg/m2/day) administered by continuous intravenous infusion for 4 days every 4 weeks and Rituximab 375 mg/m2 i.v. on day 1. HAART was given concomitantly with CT. Results: Seventy-four patients (pts) have been enrolled. The median CD4+ cell count was 161 (range 3–691) and the median Performance Status was 1 (range 0–3). Diffuse large B-cell NHL was diagnosed in 72% of pts and Burkitt in 28%. Seventy per cent of pts had advanced stage (III–IV) disease and 57% of pts had an age-adjusted international prognostic index ³2. Fifty-two out of 74 pts (70%) achieved a complete remission (cr), 4/74 (5%) had a partial remission and 18 pts progressed. With a median follow-up of 61 months, only 17% of CRs have relapsed and 41/74 pts are alive. The overall survival, disease free survival and time to treatment failure (TTF) at 5 years were 56%, 81% and 52%, respectively. Only one secondary tumor (acute leukemia) has been observed. No case of late pulmonary or cardiac toxicity has been reported. Conclusions: The combination of Rituximab and CDE in HIV-NHL treated concomitantly with HAART is very active. CR rate (70%) and TTF at 5 years (52%) are comparable to those observed in high grade NHL of the general population. Our data confirm that in HAART era a high proportion of HIV-NHL can be cured. This study was supported by ISS grants.

scholarly journals Arthroscopic Bristow: 12-Year Experience, Assessments of Safety and Effectiveness

2019 ◽  
Author(s):  
Jose Carlos Garcia
Keyword(s):  
Los Angeles ◽  
Shoulder Instability ◽  
De Novo ◽  
Mean Value ◽  
Anterior Shoulder Instability ◽  
Simple Shoulder Test ◽  
The Mean ◽  
Lateral Rotation ◽  
Clinically Significant

Abstract Objective The open Bristow procedure is a long established and effective method for treating anterior shoulder instability. Following the trends of minimally-invasive surgeries, these procedures were performed arthroscopically, and their outcomes were evaluated. Methods A total of 43 shoulders of patients submitted to Bristow procedures by arthroscopy, using a graft positioned horizontally and a screw, with at least two years of postoperative follow-up, were evaluated regarding quality of life, de novo dislocation index, and loss of lateral rotation. Results The mean follow-up time was of 76 months (range: 129 to 24 months). The University of California at Los Angeles (UCLA) score varied from 25.56 ± 0.50 (standard deviation [SD] = 3.25) to 33.23 ± 0.44 (SD = 2.91) (p < 0.0001). Two or more years after surgery, the mean Rowe score was of 94.25 ± 1.52 (SD = 1.34), whereas the good results standard is 75 (p < 0.0001). The mean value for the simple shoulder test was of 11.35 ± 0.21 (SD = 1.34), while the mean value of the lateral rotation loss was of 10.37° ± 1.36° (SD = 8.58°). There were no de novo dislocations.In total, there were 12 complications, 8 of which had no clinical repercussions. The clinically-significant complications included an infection six months after surgery with a potential hematogenous origin, a coracoid fracture that required an intraoperatively procedure change, and two patients with previous impingement who required synthesis material removal more than six months after surgery. Conclusion Although the arthroscopic Bristow procedure was effective in treating anterior shoulder instability, it is not a complication-free surgery.

scholarly journals CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 241-247 ◽  
Author(s):  
D Delia ◽  
G Cattoretti ◽  
N Polli ◽  
E Fontanella ◽  
A Aiello ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
De Novo ◽  
Cell Subset ◽  
Ultrastructural Level ◽  
Cytoplasmic Staining ◽  
Clear Cut ◽  
Hodgkin's Lymphomas

Abstract The CD1 cluster of monoclonal antibodies (MoAbs) CD1a, CD1b, and CD1c, identifies molecules that are differentially expressed on hematopoietic and nonhematopoietic tissues. Our earlier finding that the mantle zone (MZ) but not the germinal center (GC) of normal lymph nodes (LN) is CD1c+, CD1a-, and CD1b- prompted us to further investigate the expression of these molecules on normal, activated, and malignant B cells. We report that blood and spleen contain CD1c+ B cells that account for 49% +/- 20.4% (mean +/- SD) and 50.9% +/- 4.4% of the total B cell population, respectively. CD1a- and CD1b-specific MoAbs are unreactive with both B and T cells; these latter are CD1c- as well. When CD1c+ and CD1c- B cells are activated in vitro, the CD1c molecule is upregulated in the former subset and induced de novo in the latter. Conversely, activated blood T cells remain CD1c-. Neither CD1a nor CD1b molecules are detected on activated T and B lymphocytes. At ultrastructural level, the CD1c+ B cells exhibit distinctive features, namely, condensed chromatin with or without a nucleolus and a unique cluster of cytoplasmic vesicles and organelles; the number of nucleolated cells is higher in the spleen (95%) than in the tonsil (40%) or blood (5%). These findings further confirm the similarity between blood and MZ B cells. The CD1c expression assessed on 27 B-cell chronic lymphocytic leukemias (B-CLL) and 46 B non-Hodgkin's lymphomas (B-NHL) was detected on 41% and 32% of cases, respectively; the latter comprised four follicular and 11 diffuse histotypes. The Burkitt's lymphomas were CD1c-negative. The B-cell neoplasms were all CD1a- and, except for four with a weak cytoplasmic staining, all CD1b- as well. The clear-cut CD1c distribution in normal LN (MZ+, GC-) contrasted with the evidence that some B-NHL cells of GC origin (eg, follicular with predominantly small cleaved cells) were CD1c+. Overall, the finding that CD1c expression is restricted to a fraction of B cells present in lymphoid organs and in peripheral blood indicates that CD1c is a powerful marker for the identification and dissection of B-cell subsets whose functional properties can now be evaluated.

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

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3383-3385 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
Simone Lessac-Chenen ◽  
...  
Keyword(s):  
De Novo ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Second Line ◽  
Cell Of Origin ◽  
Free Survival ◽  
Significant Difference ◽  
The Common

AbstractA 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.

scholarly journals De Novo CD5+ Primary Gastrointestinal Diffuse Large B-Cell Lymphoma: Challenges With Treatment and Clinical Course

2019 ◽  
Vol 7 ◽  
pp. 232470961989354
Author(s):  
Preethi Ramachandran ◽  
Sonu Sahni ◽  
Jen C. Wang
Keyword(s):  
Gastrointestinal Tract ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Gastrointestinal Lymphomas ◽  
Large B Cell

The gastrointestinal tract is a common extranodal site for lymphomas. However, primary gastrointestinal lymphomas are rare. Diffuse large B-cell lymphomas (DLBCL) are the most commonly encountered type in the gastrointestinal tract. Most of the DLBCL are CD5 negative. CD5+ DLBCL is very rare and a poor prognostic subtype of lymphoma. We report a rare case of primary small bowel CD5+ DLBCL that evolved from being a localized low International Prognostic Index–scored disease into an advanced and aggressive disease primarily dictated by the presence of CD5 antigen positivity.

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