RISK-adapted treatment of Burkitt’s lymphomas in childern

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9034-9034
Author(s):  
T. Z. Mohran ◽  
E. N. Ebeed
Keyword(s):  
Cytosine Arabinoside ◽  
B Cell Lymphoma ◽  
Developed Countries ◽  
Burkitt’S Lymphoma ◽  
Stage I ◽  
Burkitt's Lymphoma ◽  
Stage Iii ◽  
Treatment Result ◽  
High Dose ◽  
Female Ratio

9034 Background and Purpose: Various treatment regimens have been implemented in an attempt to improveDFS of children with B cell lymphoma. We evaluates the treatment results of children with stage I, II III Burkitt’s lymphoma at 2 centers in Egypt. Patients and Methods: Patient recruitment in this open non-randomized study occurred from July 1998 to Dec 2002 . 97 patients with pathologically proven Burkitt’s lymphoma stage I to III were diagnosed . All patients were subjected to history, clinical examination, CSF, bone marrow and radiological evaluation. Patients with stage IV were excluded from. Patients with stage I and II received 4 cycles of (A→B→A→B), while patients with stage III received 8 cycles of (A→B→A→B→A→B→A→B). Intrathecals were given during the first 4 cycles. Cycle A was formed of cyclophosphamide, adriamycin, vincristine, cytosine arabinoside, plus intrathecal MTX and cytosine arabinoside. Cycle B was formed of ifosfamide, vepeside, methotrexate, vincristine and intrathecal cytosine arabinoside and mtx. Results: Patients was 97, their age ranged between 2 and 18, theirmean age was 8.6 and median was 8 years.The male to female ratio was 3.8:1. The primary site was the abdomen in 49 patients (50%), peripheral lymph node enlargement was encountered in 38 patients (39.1%). Jaw involvement occurred in 7 patients (7.2%). Two patients (2%) presented with Tonsilar mass and only one patient presented with mass at inner canthus (1%). Patients were staged according to St. Jude staging system. Patient distribution was as follows: Stage I, 18 (18.6%); stage II, 31 (32%); stage III, 48 (49.5%). In August 2003, 90 patients were in continuous complete remission with a follow up period ranged between 8 months and 53 months and a median 39 months. The projected 3 years DFS for the whole group was 93.8%±2.5%. Correlation between DFS and LDH was significant (P=0.01) while correlation with age, sex and stage was insignificant. Conclusions: Treatment result with the prescribed protocol is extremely good. The outcome of non advanced Burkitt’s lymphoma in rural areas of Egypt is comparable to all studies in developed countries. High dose methotrexate is not a must to improve survival of stage I-III Burkitt’s lymphoma. Initial serum LDH level is an important prognostic factor. Key words: Childhood, Burkitt’s lymph. No significant financial relationships to disclose.

scholarly journals Burkitt’s Lymphoma and B-Cell Lymphoma Unclassifiable With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt’s Lymphoma in Patients With HIV: Outcomes in a South African Public Hospital

2017 ◽  
Vol 3 (3) ◽  
pp. 218-226 ◽  
Author(s):  
Gerhard Sissolak ◽  
Matthew Seftel ◽  
Thomas S. Uldrick ◽  
Tonya M. Esterhuizen ◽  
Nooroudien Mohamed ◽  
...  
Keyword(s):  
South Africa ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
High Dose ◽  
Baseline Serum ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose Burkitt’s lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. Methods We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa. Differences between BL and BL/DLBCL, survival outcomes, and factors associated with survival were analyzed. Results There were 35 patients with either HIV-associated BL (24) or BL/DLBCL (11) who met study criteria. Median CD4+ T-lymphocyte count at lymphoma diagnosis was 188 cells/μL (range, 10 to 535 cells/μL). Patients with BL/DLBCL were significantly older and had less bone marrow involvement and lower baseline serum lactase dehydrogenase than patients with BL. Eighty-nine percent of patients presented with advanced disease, and 25% had baseline CNS involvement. Chemotherapy regimens consisted of cytoreduction with low-dose cyclophosphamide, vincristine, and prednisone followed by induction with vincristine, methotrexate, cyclophosphamide, doxorubicin and prednisone (LMB 86; 57%); hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (hyper-CVAD; 20%); cyclophosphamide, doxorubicin, vincristine, and prednisone and high-dose methotrexate with leucovorin rescue on day 10 with accompanying prophylactic IT chemotherapy (Stanford regimen; 14%); and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-like; 9%) regimens. Twenty-three patients received CNS treatment or prophylaxis, and 31 received concurrent combination antiretroviral therapy. Two-year overall survival was 38% (95% CI, 22% to 54%) and 2-year event-free survival was 23% (95% CI, 11% to 38%), with no difference between histologic subtypes. Common causes of death were infection (41%) and CNS disease progression or systemic relapse (41%). Conclusion Cure of HIV-associated BL and BL/DLBCL with intensive regimens is possible in resource-limited settings, but lower toxicity regimens, improved CNS prophylaxis, and increased resources for supportive care are required.

High Survival Rate in Adult Burkitt’s Lymphoma/Leukemia and Diffuse Large B-Cell Lymphoma with Mediastinal Involvement.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 518-518 ◽  
Author(s):  
Dieter Hoelzer ◽  
Wolfgang Hiddemann ◽  
Anita Baumann ◽  
Hartmut Döhner ◽  
Ulrich Dührsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Relapse Rate ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Stage Iii ◽  
High Survival ◽  
Cns Relapse ◽  
Mediastinal Involvement

Abstract With short intensive chemotherapy mainly based on HDMTX, fractionated alkylators and HDAC outcome of Burkitt’s NHL and mature B-ALL (B-ALL) in adults could be improved substantially to CR rates of 80% and overall survival (OS) of 50–70% (Hoelzer et al, Blood, 1996). Further intensification - namely increase of MTX dose - failed to improve these results. Therefore the German Multicenter Study Group for Adult ALL (GMALL) invented in 2002 a new protocol for mature B-ALL/Burkitt and other high-grade NHL, namely primary mediastinal (med) DLBCL, including 6x Rituximab® 375 mg/m2 before each chemo cycle and two R maintenance cycles. In addition 2 cycles based on HDAC 2 g /m2 were included. HDMTX was 1,5 g/m2 in the protocol for younger pts (<55 yrs). Older pts (>55 yrs) received a dose reduced regimen without HDAC and with MTX at 500 mg/m2. 227 pts with Burkitt (27=Burkitt-like), B-ALL or med DLBCL aged between 16 and 78 enrolled between 09/02 and 12/06 were evaluable for response after the first two cycles. The median age was 36 yrs for Burkitt, 46 for B-ALL and 35 for med DLBCL; 18%, 41% and 12% were older than 55 yrs respectively. The subgroups were characterised as follows: 115 Burkitt (stage III–IV 52%, extranodal inv. 78%, aaIPI >1 47%), 70 B-ALL, 42 med DLBCL (stage III–IV 55%, extranodal inv. 71%, aaIPI >1 61%). The CR rate was 90% in Burkitt, 83% in B-ALL and 69% in med DLBCL; death under therapy occurred in 3%, 11% and 0% respectively. The overall survival at 3 yrs was 91% for Burkitt, 79% for B-ALL and 90% for med DLBCL in pts at the age of 15–55 yrs and 84%, 39% and 67% (N=5) respectively in pts >55 yrs. CNS relapses were observed in 3 out of 22 older CR patients with B-ALL whereas in younger pts the CNS relapse rate was 0. CNS relapses are among the reasons for inferior outcome in elderly B-ALL in contrast to elderly pts with Burkitt or med DLBCL. CNS relapse rate may hopefully be reduced by inclusion of an intermediate dose ARAC cycle in the elderly B-ALL. There was no difference in OS between pts with Burkitt (92%) vs Burkitt-like NHL (86%). Since no prognostic factors could be identified in younger pts, there was no need for SCT in CR1. Major grade III/IV toxicity was hematological (28–37%) and mucositis (36%, 37%, 28% in cycles A1, B1, C1 respectively). Compared to the previous GMLL trial B-NHL90 (without Rituximab) with 270 pts the OS of 272 patients (including LBL, LCAL, DLBCL) at 3 yrs improved significantly from 54% to 80% (p<.0001) overall, 56% to 85% (p<.0001) in younger and 39% to 65% (p=.01) in older pts. In this largest prospective study of adult Burkitt’s lymphoma/leukemia and med DLBCL the combination of Rituximab and 6 short intensive chemo cycles was feasible and lead to an OS of 90% in NHL and 79% in mature B-ALL in the younger patient cohort. Even in older pts with Burkitt’s NHL survival was 84%. The further aim is now to reduce toxicity, namely mucositis.

Efficacy of a Brief, Cyclophosphamide-Intensive Regimen for Older Patients with Newly Diagnosed Burkitt's or Atypical Burkitt's Lymphoma/Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2685-2685
Author(s):  
Yvette L. Kasamon ◽  
Robert A. Brodsky ◽  
Michael J. Borowitz ◽  
Pamela A. Crilley ◽  
Richard F. Ambinder ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Older Patients ◽  
Research Funding ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 2685 Poster Board II-661 Background: Although standard therapies cure most adolescents and young adults with Burkitt's lymphoma/leukemia (BL), older patients (pts) have an inferior prognosis with an estimated 1-year survival of 50%. The inferior outcome is attributable to both insufficient efficacy and excess toxicity. Cyclophosphamide (Cy) has long been recognized to be arguably the most active agent in BL. Prior work at our institution showed that high-dose Cy, equivalent to transplantation doses, could be given without stem cell rescue with minimal toxicity even in older pts. Patients and Methods: A phase II trial for pts age ≥ 30, based on intensive Cy and incorporating rituximab but no anthracycline, was developed with a primary endpoint of 1-year overall survival. Entry requirements included newly diagnosed BL or atypical BL; any performance status (PS); HIV negative; and no significant cardiac dysfunction. Renal failure, even if necessitating dialysis, was permitted if it was acute. Treatment consisted of 3 cycles, with successive cycles beginning on day 15 or when ANC was ≥ 500/μL. Cycles 1 and 2 consisted of Cy 1500 mg/m2 IV day 1; vincristine 1.4 mg/m2 (2 mg cap) day 1; prednisone 100 mg days 1-5; rituximab 375 mg/m2 IV days 1 and 8; methotrexate 3 g/m2 IV day 8 with leucovorin rescue; cytarabine 100 mg intrathecally days 1, 4, and 11; and filgrastim. Cycle 3 consisted of rituximab 375 mg/m2 IV day 1; high-dose Cy (50 mg/kg IV days 2, 3, 4, and 5) with uroprotection; filgrastim; and rituximab 375 mg/m2 IV weekly for 4 weeks once ANC was ≥ 1000/μL. Eligibility for cycle 3 included ECOG PS < 4; no disease progression or uncontrolled meningeal disease; not on dialysis; and transaminases ' 5X upper limit of normal. Results: A prespecified interim analysis of the first 12 of a planned 20 evaluable pts is presented. Diagnosis was BL in 8 and atypical BL/unclassifiable high-grade lymphoma with features intermediate between BL and diffuse large B-cell lymphoma in 4. Median age was 56 (range 34 – 75), 8/12 (67%) had Ann Arbor stage III/IV disease, and all were high-risk by Magrath's criteria. PS ranged from 0 to 4. Two pts received hemodialysis on presentation. For all pts, actuarial event-free survival and overall survival (Figure) are 66% and 75%, respectively, at both 1 year and 2 years after treatment initiation. Three pts died during cycle 1: tumor lysis syndrome on day 1, neutropenic sepsis on day 8, multiorgan failure on day 46 after respiratory arrest on day 20. All of the other 9 pts completed protocol therapy: 8 (89%) achieved anatomic CR/CRu as well as a complete metabolic response by PET, and are event-free at a median of 29 months (range < 1 – 44 months) after therapy completion. The remaining pt had residual marrow disease followed by progression and is in remission 1 year after myeloablative allogeneic BMT. Adverse events in these 9 pts included 7 neutropenic fevers; 1 non-neutropenic bacteremia; and 1 self-limited episode of pericarditis with rapid atrial fibrillation. Grade 3 peripheral neuropathy was limited to 2 pts. The planned dose intensity was achievable: median time to cycle 2 was 15 days (14 – 21), and median time from start of cycle 1 to start of cycle 3 was 31 days (28 – 35). Median time to neutrophil recovery after the last dose of Cy was 16 days (10 – 21); median time to platelets ≥ 20,000/μL, without transfusion in the preceding week, was 22 days (0 – 30). Early stopping criteria for response or all-cause mortality have not been met. Conclusion: A very short regimen based on intensive Cy without anthracycline produces a high rate of durable CR's in older, poorer-risk pts with BL or atypical BL. Disclosures: Kasamon: Genentech: Research Funding. Swinnen:Genentech: Consultancy, Research Funding; Enzon: Consultancy; Abbot: Consultancy, Research Funding.

HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.

1991 ◽  
Vol 9 (1) ◽  
pp. 133-138 ◽  
Author(s):  
M R Schwenn ◽  
S R Blattner ◽  
E Lynch ◽  
H J Weinstein
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Transverse Myelitis ◽  
Stage Iv ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Stage Iii ◽  
High Dose ◽  
Cell Acute Lymphoblastic Leukemia

We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.

Primary and Secondary Central Nervous System Lymphoma: Outcomes from Houston Methodist Cancer Center

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Cesar Gentille Sanchez ◽  
Ethan Burns ◽  
Ibrahim Muhsen ◽  
Humaira Sarfraz ◽  
Carlo Guerrero ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cancer Center ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Female Ratio ◽  
Multiagent Chemotherapy

Introduction Primary Central Nervous System Lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin Lymphoma (NHL), with diffuse large B-cell Lymphoma (DLBCL) reported in 90% of cases. Secondary CNS lymphoma (SCNSL) may occur as an isolated recurrence of previously diagnosed NHL or occur simultaneously as a manifestation of systemic disease. Comparative data on survival in treated PCNSL and SCNSL in the real-world setting is lacking. We present a retrospective analysis of outcomes in PCNSL and SCNSL patients treated at the Houston Methodist Cancer Center. Methods We retrospectively identified patients with a diagnosis of PCNSL or SCNSL from 2015 to 2020. Data collected included age, race, sex, diagnosis (PCNSL, SCNSL), histology and immunohistochemistry, treatment type (chemotherapy, radiation), transplant rates as well as outcomes (alive/dead). Responses were classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Survival was analyzed using Kaplan-Meier methodology, and log-rank tests were used to compare survival distributions. P &lt; 0.05 was considered statistically significant. Results There were 50 patients with CNS lymphoma identified between 2015 and 2020; 68% were PCNSL. Out of 43 with available pathology, 2 patients were T-cell lymphomas and 41 DLBCL. Out of the DLBCL cases, 95% of cases expressed CD20 while close to 60% were positive for MUM1, bcl-2 and bcl-6. Less than 15% of cases were positive for CD10. CD30 was positive in 17% of cases. Cerebral hemispheres (76%) was the most common organ involved, followed by ocular (8%), intraventricular space (6%) and cerebellum (6%). Median age at diagnosis was 67 years; male to female ratio was 1.27. Caucasian (62%) and Hispanic (24%) were most common ethnicities. Epstein-Barr Virus was positive in 14% of patients (5 in PCNSL and 2 in SCNSL). One patient with SCNSL had human immunodeficiency virus. The median follow-up time was 9.1 months. Multiagent chemotherapy including high dose methotrexate (MTX), cytarabine and rituximab was given to 48% of the patients while 32% received high dose MTX alone plus rituximab. From the latter group, five out of sixteen patients received temozolomide. Other regimens were used in 6% of the cases. Median dose of MTX in a multiagent chemotherapy regimen was 2.5gr/m2 and 2.25gr/m2 when used alone or with temozolomide. Median number of cycles given was 3. Radiation therapy alone was given to 8% of cases. Three patients did not receive treatment. For patients with PCNSL, overall response rate (ORR) was 82.8% (CR 65.5%, PR 13.8%, SD 3.4%). ORRs were similar between multiagent chemotherapy and methotrexate alone (+/- temozolomide) with 86.7% and 83.3% respectively. ORR for SCNSL was 57.1% (CR 35.7%, PR 21.4%); only 1 patient was treated with MTX alone. Further lines of therapy were required in 9.3% of patients. Consolidation with whole brain radiation was given in 22% of the cases (29.4% for PCNSL and 6.3% for SCNSL). Autologous stem cell transplant was performed in 10% of the patients (2 PCNSL, 3 SCNSL). Overall survival for patients with PCNSL was 74.8 months and 10.1 months for SCNSL (p=0.0444) (Figure 1). Survival was not significant between patients receiving multiagent chemotherapy and MTX alone or in combination with temozolomide (3-year OS 57.3% vs 73.4%, p= 0.5652) (Figure 2). Conclusion Most patients diagnosed with PCNSL are non-germinal center DLBCL. Median MTX dose was lower than 3gr/m2 with excellent ORR of over 80% in PCNSL. Response rates were lower in SCNSL and in general, patients with PCNSL had better outcomes. Survival did not differ significantly between regimens, suggesting that a lower intensity therapy may perform similarly to multiagent chemotherapy. These results need to be confirmed by prospective studies. Disclosures No relevant conflicts of interest to declare.

Chloroquine Inhibits Autophagy, Enhances p53-Dependent Apoptosis, and Delays Tumor Recurrence in a Mouse Model of B Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2421-2421 ◽  
Author(s):  
Ravi K. Amaravadi ◽  
Duonan Yu ◽  
Andrei Thomas-Tikhonenko ◽  
Craig B. Thompson
Keyword(s):  
Mouse Model ◽  
Fusion Protein ◽  
B Cell ◽  
Nuclear Localization ◽  
Target Genes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Recurrent Tumors

Abstract Burkitt’s lymphoma is an example of an aggressive B cell neoplasm characterized by overexpression of the c-myc oncogene and frequent inactivation of the tumor suppressor gene p53. A non-transgenic mouse model of Burkitt’s lymphoma was generated by retroviral transduction of the human c-myc gene into bone marrow cells derived from the p53-estrogen receptor (p53ER) knock-in mouse. The resulting myc/p53ER cells produce an aggressive B cell lymphoma when injected subcutaneously into the flanks of syngeneic mice. When tumor-bearing mice are treated with tamoxifen intraperitoneally, the p53ER fusion protein is targeted to the nucleus where p53-dependent apoptosis can take place. On successive in vivo passages, cells develop the ability to survive p53 activation and escape p53ER-dependent apoptosis despite tamoxifen treatment and nuclear localization of the p53ER fusion protein. We hypothesized that cells resistant to p53-dependent apoptosis utilize autophagy as an essential survival mechanism. Thus, these tumors could be sensitive to chloroquine, a lysosomotropic inhibitor of autophagy that has been used extensively in humans as an antimalarial and for the treatment of rheumatoid arthritis. Daily intraperitoneal chloroquine or hydroxychloroquine treatment of mice bearing myc/p53ER tumors in the absence of tamoxifen resulted in a delay in tumor growth. When tamoxifen was added to induce nuclear localization of p53ER, mice that received tamoxifen plus chloroquine had a complete tumor response while mice that received tamoxifen plus saline had transient tumor shrinkage followed quickly by regrowth. Tamoxifen plus chloroquine treatment enhanced the expression of p53-dependent target genes and increased caspase activation compared to tamoxifen plus saline treatment. A higher percentage of cells in tumors treated with tamoxifen plus chloroquine underwent apoptosis compared to tumors treated with tamoxifen plus saline. Moreover, tumors that recurred in the mice treated with daily tamoxifen plus chloroquine did so after a significantly longer latency period then mice treated with tamoxifen plus saline. Recurrent tumors showed loss of expression of p53 target genes. Electron microscopy of recurrent tumors confirmed the accumulation of vacuoles in chloroquine treated tumors compared to controls, suggesting inhibition of lysosome function leads to the accumulation of ineffective autophagic vacuoles. These results indicate that inhibiting autophagy with lysosomotropic chloroquine derivatives could be a useful therapeutic addition to treatment regimens for aggressive B cell lymphomas.

Effect of Adding Rituximab (R) to Induction Treatment and High Dose Chemotherapy (HDC) Prior to Autologous Stem Cell Transplantation (ASCT) as First Line Therapy in Stage III-IV Diffuse Large B-Cell Lymphoma (B-DLCL) at Poor Prognosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 676-676
Author(s):  
Umberto Vitolo ◽  
Giuseppe Rossi ◽  
Maria Giuseppina Cabras ◽  
Anna Marina Liberati ◽  
Annalisa Chiappella ◽  
...  
Keyword(s):  
Germinal Center ◽  
Poor Prognosis ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Induction Treatment ◽  
Control Group ◽  
High Dose ◽  
Study Group ◽  
First Line ◽  
Bulky Disease

Abstract Introduction: We investigated efficacy and safety of adding Rituximab (R) to induction and intensified HDC as part of first line treatment in pts with aa-IPI at Intermediate-High (IH) or High (H) risk with B-DLCL at diagnosis. We compared two groups of similar pts enrolled in two consecutive non-randomized phase II clinical trials with up-front HDC and ASCT with or without R with identical inclusion criteria conducted by GIMURELL. Patients and methods: 118 previously untreated pts <61 years with B-DLCL, stage III-IV at aaIPI IH or H risk were treated: 41 pts were enrolled into HDC trial (control group; August 1991-August 1995) and 77 pts into R-HDC trial (study group; January 2001-December 2004). Treatment in R-HDC study group consisted in an induction treatment lasting two months with four courses of R-MegaCEOP chemotherapy (R 375 mg/m2 day1, CTX 1200 mg/m2 + EPI 110 mg/m2 + VCR 1.4 mg/m2 day3 and PDN 40 mg/m2 days 3–7) every 14 days with G-CSF support; then two courses of intensified chemoimmunotherapy R-MAD (Mitoxantrone 8 mg/m2 + ARAC 2000 mg/m2/12h + Dexamethasone 4 mg/m2/12h for 3 days and R 375 mg/m2 day4 and before PBSC harvest) followed by ASCT with BEAM as conditioning regimen. Treatment in HDC control group consisted in an induction treatment lasting two months with MACOPB chemotherapy x 8 weekly infusions followed by the same intensified and HDC regimens (MADx 2 courses + BEAM and ASCT). All pts were given antibacterial and antifungal prophylaxis throughout the whole treatment. IF RT was given to areas of previous bulky disease in both trials. Results: Pts characteristics in both trials were comparable with no statistically significant differences: median age was 45 years (19–60); 51% were at H risk; 36% had bone marrow (BM) involvement, 80% had LDH level >normal and 42% extranodal sites>1. Complete Response at the end of the treatment was: 60 pts (78%) in R-HDC group and 28 (68%) in HDC group (p=.25). Failures (17% vs 24%) and toxic deaths (5% vs 7%) were comparable between the two groups (R-HDC vs HDC). Short-term toxicity appeared similar. Median follow-up was 27 months in study group and 69 months in control group. Two-year failure-free survival (FFS) and 2-yr overall survival (OS) rates in R-HDC group compared to HDC group were: FFS 70% vs 49% (p=.036); OS 78% vs 56% (p=.009). A better outcome for pts treated with R-HDC was confirmed in both IPI groups (IH and H risk). A Cox’s model was performed to adjust the effect of treatment for competing risk factors (age, IPI, BM involvement, number of extranodal sites). In this multivariate analysis the risk of failure and death was confirmed as significantly reduced in R-HDC group: adjusted hazard ratio (R-HDC vs HDC) was 0.54 (95% CI=0.30–0.98, p=.02) for FFS and 0.42 (95% CI=0.21–0.84, p=.03) for OS. Germinal center and non germinal center subtype analysis is ongoing in both treatment groups. Conclusions: these results suggest that the addition of Rituximab to induction and intensified chemotherapy before BEAM and ASCT is effective and safe in B-DLCL at poor prognosis improving the outcome of these pts.

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