Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma.

1992 ◽  
Vol 10 (12) ◽  
pp. 1870-1878 ◽  
Author(s):  
B De Bernardi ◽  
M Carli ◽  
F Casale ◽  
P Corciulo ◽  
L Cordero di Montezemolo ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Tumor Regression ◽  
Standard Dose ◽  
Autologous Bone Marrow Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Cooperative Group ◽  
Complete Excision ◽  
Treatment Protocols ◽  
Poor Risk

PURPOSE The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma. PATIENTS AND METHODS From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT). RESULTS Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5). CONCLUSION Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.

Impact of Three Courses of Intensified CHOP Prior to High-Dose Sequential Therapy Followed by Autologous Stem-Cell Transplantation As First-Line Treatment in Poor-Risk, Aggressive Non-Hodgkin's Lymphoma: Comparative Analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40

2005 ◽  
Vol 23 (16) ◽  
pp. 3793-3801 ◽  
Author(s):  
Gustaaf W. van Imhoff ◽  
Bronno van der Holt ◽  
Marius A. MacKenzie ◽  
Mars B. van′t Veer ◽  
Pierre W. Wijermans ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Sequential Therapy ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Cooperative Group ◽  
Free Survival ◽  
Poor Risk

Purpose Timing, appropriate amount, and composition of treatment before high-dose therapy and autologous stem-cell transplantation (ASCT) in patients with poor-risk, aggressive non-Hodgkin's lymphoma (NHL) are still unknown. We conducted two consecutive multicenter phase II trials with up-front, high-dose, sequential chemotherapy and ASCT in poor-risk, aggressive NHL. Both trials had identical inclusion criteria and only differed in amount and duration of induction treatment before ASCT. Patients and Methods Between 1994 and 2001, 147 newly diagnosed, poor-risk, aggressive NHL patients, age ≤ 65 years with stage III to IV and lactate dehydrogenase (LDH) more than 1.5× upper limit of normal (ULN), entered the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) -27 and HOVON-40 trials. Treatment in HOVON-27 consisted of two up-front, high-dose induction courses followed by carmustine, etoposide, cytarabine, and melphalan plus ASCT in responding patients. In HOVON-40, the same treatment was preceded by three intensified courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Results Patient characteristics in both trials were comparable: 80% had diffuse large B-cell lymphoma, 77% had stage IV disease, and median LDH levels were 3.1× ULN. Complete remission (CR) in both trials was 45% to 51%. Before ASCT, CR was 14% in HOVON-27 versus 28% in HOVON-40 (P = .03). Treatment failure was similar (27%). Four-year survival estimates in HOVON-27 compared with HOVON-40 were overall survival, 21% v 50% (P = .007); event-free survival, 15% v 49% (P = .0001); and disease-free survival, 34% v 74% (P = .008). This different outcome favoring HOVON-40 remained highly significant when correcting for competing risk factors in multivariate analysis. Conclusion In patients with poor-risk, aggressive NHL, addition of intensified CHOP before up-front, high-dose, sequential therapy and ASCT significantly improved the duration of response and survival.

Điều trị tăng liều Imatinib trên bệnh nhân u mô đệm đường tiêu hoá giai đoạn muộn tiến triển sau điều trị bước 1 liều chuẩn

2020 ◽  
Author(s):  
Kien Do Hung
Keyword(s):  
Primary Tumor ◽  
Standard Dose ◽  
Performance Status ◽  
Gastric Tumor ◽  
High Dose ◽  
Time To Failure ◽  
Gastrointestinal Stromal Tumours ◽  
Mean Time To Failure ◽  
The Mean ◽  
Mean Time

Objective: Evaluating the result of high-dose imatinib for metastatic gastrointestinal stromal tumours after failure standard-dose first line. Patients and method: Restrospective analysis of 46 patients with metastatic gastrointestinal stromal tumours after failure standard-dose imatinib treated with high-dose imatinib at K hospital from 1/2015 đến 10/2019. Results: Median age was 54.6±9.5, male was 58.7%. The common primary tumor was gastric tumor. The mean time to failure of imatinib standard-dose 400mg/day was 38.2±5.3 months. Liver lesions were the most common lesions progressed after imatinib standard-dose failure (71.7%), primary tumor progressed was 39.1%. There was no patient who had complete response with treatment, the proportion of partial response accounted for 21.7% and stable disease was 45.7%. The clinical benefit rate was 67.4%. The sex-female, primary gastric tumor, good ECOG performance status, neutrophils, hemoglobine and albumin before treatment were the significant prognostic factors affecting the treatment response, p &lt;0.05. The mean time to failure was 22.5 ± 3.4 (months), (min: 2.0; max: 58.0), median was 11.0 months. Conclusion: Treatment of high-dose imatinib after failure standard-dose 400mg/day showed the efficacy and good tolerance in metastatic GISTs.

Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission.

1992 ◽  
Vol 10 (4) ◽  
pp. 644-646 ◽  
Author(s):  
L F Verdonck ◽  
A W Dekker ◽  
G C de Gast ◽  
H M Lokhorst ◽  
H K Nieuwenhuis
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Lymphoblastic Lymphoma ◽  
Adult Patients ◽  
High Dose ◽  
Consolidation Therapy ◽  
Poor Risk ◽  
First Remission ◽  
Autologous Bone

PURPOSE Adult patients with poor-risk lymphoblastic lymphoma (LBL) treated with intensive multiagent chemotherapy (acute lymphoblastic leukemia [ALL]-like regimens) have a poor prognosis, with a disease-free long-term survival rate of less than 20%, caused by a very high relapse rate. Thus, adult patients with poor-risk LBL are candidates for alternative intensive consolidation therapy. PATIENTS AND METHODS Nine adult patients with poor-risk LBL in first remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; six patients) or ALL-like regimens (three patients), were treated with high-dose cyclophosphamide and total body irradiation (TBI) followed by nonpurged autologous bone marrow transplantation (ABMT). RESULTS Two of nine patients relapsed at 4 and 8 months, respectively, after BMT, and one patient died of acute myeloblastic leukemia (AML) 7 months after ABMT without recurrence of his lymphoma. Six patients are in unmaintained first remission with a follow-up of 12 to 113 months (median, 53 months) after transplantation. CONCLUSIONS These results suggest that intensive consolidation therapy with high-dose cyclophosphamide and TBI followed by nonpurged ABMT may improve the long-term prognosis of this disease.

Autologous bone-marrow transplantation: host effects of high-dose BCNU.

1983 ◽  
Vol 1 (10) ◽  
pp. 610-620 ◽  
Author(s):  
T Takvorian ◽  
L M Parker ◽  
F H Hochberg ◽  
G P Canellos
Keyword(s):  
Bone Marrow ◽  
Pulmonary Toxicity ◽  
Cardiac Toxicity ◽  
Liver Toxicity ◽  
Tumor Regression ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Autologous Bone

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.

A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients.

1990 ◽  
Vol 8 (7) ◽  
pp. 1239-1245 ◽  
Author(s):  
J P Eder ◽  
A Elias ◽  
T C Shea ◽  
S M Schryber ◽  
B A Teicher ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Standard Dose ◽  
Autologous Bone Marrow Transplantation ◽  
Maximum Tolerated Dose ◽  
Cross Resistance ◽  
Testis Cancer ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Dose Therapy

The principles of dose-response and combination chemotherapy were basic to the design of the initial curative standard-dose treatment regimens for leukemias, lymphomas, and testis cancer. Agents were selected with different dose-limiting toxicities, resulting in subadditive toxicity in combination. A fourth principle in the design of curative regimens was to combine agents with different mechanisms of action to avoid cross-resistance. Based on these principles, combinations of the highest tolerated doses of active noncross-resistant agents are required to decrease the emergence of drug resistance and achieve optimum cytotoxicity. Hematopoietic stem-cell support provides a mechanism for significantly increasing the doses of active agents, a strategy that has resulted in the cure of 10% to 50% of selected patients with lymphoma who could not be cured with standard-dose therapy. The lack of sufficiently effective cytoreductive conditioning regimens remains the major impediment to improving the high-dose therapy of patients with solid tumors. In this study, 27 patients with solid tumors were treated with a combination of cyclophosphamide, thiotepa, and carboplatin (CTCb) in a phase I-II study. Severe mucositis and neurotoxicity were dose-limiting. The maximum-tolerated dose (MTD) of the combination was 6.0 g/m2 of cyclophosphamide, 500 mg/m2 of thiotepa, and 800 mg/m2 of carboplatin. There were two deaths (7%) of sepsis, and an overall response rate of 72% in refractory tumors (81% in breast cancer). CTCb is a combination with low morbidity and high cytoreductive efficacy designed to exploit the principles of curative cancer chemotherapy.

Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.

1993 ◽  
Vol 11 (9) ◽  
pp. 1770-1779 ◽  
Author(s):  
A Garaventa ◽  
B De Bernardi ◽  
C Pianca ◽  
A Donfrancesco ◽  
L Cordero di Montezemolo ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Standard Dose ◽  
Serum Lactate ◽  
Response To Therapy ◽  
Serum Lactate Dehydrogenase ◽  
Risk Category ◽  
High Dose ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Response To Chemotherapy

PURPOSE To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.

Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases.

1991 ◽  
Vol 9 (6) ◽  
pp. 962-969 ◽  
Author(s):  
G Dini ◽  
E Lanino ◽  
A Garaventa ◽  
D Rogers ◽  
S Dallorso ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Partial Remission ◽  
Autologous Bone Marrow Transplantation ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Free Survival ◽  
Autologous Bone

From October 1984 to November 1987, 34 patients aged from 1 year 1 month to 7 years 7 months with resistant or relapsed neuroblastoma (NB) (group 1, 10 patients), unselected disseminated NB (group 2, 14 patients), or selected disseminated NB (group 3, 10 patients) received myeloablative therapy (MAT) followed by unpurged autologous bone marrow transplantation (ABMT) at the end of an intensive protocol, which included high-dose chemotherapy and surgery to the primary tumor. Median time from diagnosis to MAT and ABMT was 6 months (5 months from last relapse to MAT and ABMT in the relapsed patients). The MAT regimen included vincristine, fractionated total body irradiation (TBI), and melphalan. Seventeen patients were grafted in complete remission (CR), five in very good partial remission (VGPR), 10 in partial remission (PR), and two in progressive disease (PD). The acute toxic death rate was 2.9%. The overall progression-free survival was 29%. The median progression-free survival was 20 months for the 17 patients grafted in CR, 6 months for the five patients grafted in VGPR, and 12 months for the 10 patients grafted in PR.

High-Dose Imatinib Mesylate Treatment in Patients (Pts) with Previously Untreated Early Chronic Phase (CP) Chronic Myeloid Leukemia (CML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 999-999 ◽  
Author(s):  
Jorge Cortes ◽  
Moshe Talpaz ◽  
Susan O’Brien ◽  
Francis Giles ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Standard Dose ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
P Value ◽  
High Dose ◽  
Free Survival ◽  
Clinical Observations ◽  
Pre Treatment ◽  
Grade 3

Abstract Imatinib has become the treatment of choice for most with CML. The standard dose (SD) for CP CML is 400 mg daily, but pre-clinical and clinical observations suggest that higher doses (HD) may be more effective. We have treated 222 with previously untreated CML in early CP with imatinib in 3 consecutive trials: one using SD imatinib (400 mg/day) (n=50; all entered in April 2001) and 2 subsequent trials using 400 mg twice daily (total dose 800 mg/day) (n= 172; from June 2001 until present). The 2 HD trials had identical inclusion criteria and will be considered together for this analysis. Pts followed for at least 3 months (mo) are evaluable (n=210) for this report (n=49 at 400mg, 161 at 800 mg). The median age was 48 years (range, 15 to 84); platelets were >450 x109/L in 71 pts (34%), 78 (37%) had peripheral blood (PB) blasts, and 11 (5%) had clonal evolution. Sokal risk group classification was good in 128 (61%) pts, intermediate in 61 (29%) pts, and poor in 21 (10%) pts. There was no difference in pre-treatment characteristics between the standard SD and HD groups. The results at 18 months are as follows: Response % Response p value* 400 mg/day 800 mg/day CR=Complete remission, Molecular Major=BCR-ABL/ABL <0.05%, Molecular CR=BCR-ABL undetectable (confirmed by nested PCR), *p value by log-rank Median follow-up (months) 36 19 Cytogenetic CR 81 96 0.0002 Cytogenetic Major 99 93 0.15 Molecular Major 47 67 0.0007 Molecular CR 8 24 0.02 Four pts treated with SD have transformed (3 to BP, 1 to AP) and 3 (2 to BP, 1 to AP) in the HD groups (p=0.05) (median time to transformation 11 mo, range 3 to 27). Estimated progression-free survival at 12 mo is 92% in the SD group and 99% in the HD group (p=0.42) (p=0.12 for the estimated transformation-free-survival, 94% and 99% for SD and HD at 12 mo). 4 have died (1 in SD and 3 in HD). Extramedullary toxicity was similar in the 2 groups, but myelosuppression was more common with HD, with grade ≥3 anemia, neutropenia and thrombocytopenia occurring in 7%, 39%, and 27% of pts receiving HD, respectively, and 4%, 20% and 12% of pts receiving SD. At 12 mo, the median actual dose for the HD group is still 800mg, with 40/112 (36%) evaluable having required dose reduction. This compares with 7/43 (14%) of those treated with SD. We conclude that high-dose imatinib results in higher rates of complete cytogenetic and molecular remissions, with some increase in myelosuppression.

High Dose (HD-AraC) vs Standard Dose Cytosine Arabinoside (SD-AraC) during Induction in Acute Myelogenous Leukemia (AML): Impact on Stem Cell Mobilization after Consolidation and on Autologous Transplantation (Second Report of the EORTC-Leukemia Group (LG) - GIMEMA AML-12 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 609-609
Author(s):  
Roelof Willemze ◽  
Stefan Suciu ◽  
Franco Mandelli ◽  
T.M. de Witte ◽  
Boris Labar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Autologous Transplantation ◽  
Early Death ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
No Donor ◽  
Platelet Recovery ◽  
Poor Risk

Abstract The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/m2/12 hrs for 4 days) with daunorubicin (50 mg/sqm for 3 days) and etoposide (50 mg/sqm for 5 days) vs SD-AraC (100 mg/sqm for 10 days) with the same drugs. Patients (pts) in complete remission (CR) received consolidation (Co) consisting of AraC (500 mg/sqm/12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A 2nd randomization was performed after Co in pts without a donor: auto-SCT followed or not by low dose IL-2. From 9 1999 till 7 2006, 1675 AML pts (APL excluded), age &lt;61 years, from 67 centers (23 EORTC-LG and 44 GIMEMA) entered. Currently 1571 pts have been randomized for induction and 429 pts post-Co. During the induction toxicity was similar in the 2 arms except for conjunctivitis: 6% (HD-AraC) vs 0% (SD-AraC). HD-AraC given in the induction had no impact on the organ toxicity during Co but platelet recovery (&gt; 50x109/l) was longer (median 4.0 vs 3.3 weeks; P=0.01). Among 886 pts randomized until 7 2005 by EORTC centers and 6 large GIMEMA centers, median follow-up of 2.5 years, 815 were evaluable for response. Out of 643 pts who reached CR, 57 went off study (toxicity, early progression). Among the remaining 586 who received Co, 37 could not be evaluated (early death/relapse, too early) and 549 were still CR after Co: 297 pts had no donor/no sibling, 197 had a donor and 55 were not typed. In these 3 groups the present estimates of the SCT rates are: 63% (auto-SCT), 71% (allo-SCT) and 69% (auto-SCT), resp. The 2.5-yr DFS rates (SE%) were 45% (3%), 61% (4%), and 67% (7%), resp. In pts &lt; 50 yrs, 216 pts had no donor/no sibling, 135 had a donor and 14 have not been typed. For the first 2 groups, the 2.5 yr DFS rates (SE%) were 50% (4%) vs 68% (4.5%), hazard ratio=0.64, 95% CI (0.44, 0.93), P=0.02. In pts without a donor/a sibling successful mobilization of blood stem cells (b-SC) after Co was in HD-Ara-C vs SD-Ara-C arm 53 vs 69%, of failure/postponement 37 vs 24%, and other 9.5 vs 7%. The rate of auto-SCT was similar (65 vs 64%), but harvest of BM cells was more often required in the HD-AraC group (15 vs 4.5%). Pts with an insufficient/delayed b-SC harvest had a longer (P&lt;0.001) platelet recovery (&gt; 50x109/l) after Co than those with a successful harvest: median = 6.7 vs 3.3 wks. Among 393 pts with information on cytogenetics, 14% had good risk, 50% normal, 23% other and 13% poor risk (-5/5q-, -7/7q-, complex). The 2.5-year EFS (no CR, time to relapse or death in CR) rates (SE%) were 68% (7%), 42% (4%), 32% (5%) and 14% (5%), resp. So far: toxicity of HD-Ara-C was acceptable; in those who received HD-AraC in induction platelet recovery after Co was longer and the rate of successful b-SC collection was lower; SCT rates are high and similar in the 2 randomized arms; pts &lt;50 yrs with a donor do have a longer DFS; pts with poor risk cytogenetics continue to have a poor prognosis.

Radioimmunotherapy (RIT) with 90yttrium Zevalin Followed by BEAM Conditioning Regimen (Z-BEAM) and Autologous Stem Cell Transplantation (ASCT) for the Treatment of High Risk Relapsed/Resistant Non Hodgkin's Lymphoma (NHL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3107-3107
Author(s):  
Barbara Botto ◽  
Chiara Ciochetto ◽  
Marilena Bellò ◽  
Roberto Passera ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Matched Pair ◽  
High Dose ◽  
Bulky Disease ◽  
Response Status

Abstract Abstract 3107 High dose chemotherapy (HDC) and ASCT is actually considered an effective treatment for relapsed NHL. Standard dose Zevalin (0.4 mCi/kg) combined with conventional BEAM (Z-BEAM) is a promising conditioning regimen for the treatment of high risk relapsed/resistant NHL. We evaluated the feasibility and the efficacy of Z-BEAM in a group of relapsed/refractory patients treated in a single institution. Between October 2006 and December 2010 twenty nine pts were treated with Zevalin (day –14) followed by standard dose BEAM (day –7 to –1) and ASCT. Patients were included into the study and considered at high risk of failure if showed: progression or early relapse (<1 year) from previous therapy or multiple relapses. Rituximab followed by standard dose DHAP or ICE were used as debulking and mobilizing schedule. Clinical characteristics were as follows: 14 refractory and 15 early or multiple relapse; 8 grade I-II follicular, 16 PML/DLBCL, 3 MCL, 2 indolent non follicular; 6 stage II and 23 stage III-IV; 10 patients had bulky disease and 15 bone marrow involvement; 9 LDH level above normal. 13 patients received only one previous line of treatment and 16 were treated with 2 or more lines before Z-BEAM, all containing Rituximab. Only 5/29 patinets received a reducted dose of 0.3 mCi/kg Zevalin because of low platelets counts. Response status before RIT was: 14 CR (49%), 9 PR (33%), 3 SD (9%) and 3 PD (9%). At the end of treatment response status is actually available in 26/29 pts: CR 18(69%), PR 5(19%) and PD 3 (12%). Overall response rate was converted from 81% before Z-BEAM and ASCT to 88% at the end of the entire program. Median CD34+ cells infused was 7.26 106/kilograms (range 4.43–8.9). All pts engrafted with median time to platelet and neuthrophils count higher than 20×109/l and 0.5×109/L of 11 and 10 days respectively. Febrile neutropenia occurred in 12/29 pts. One pulmonary Aspergillosis and 8 bacteriemia were documented. One patient experienced an intestinal perforation during aplasia and one cardiac failure was documented in a woman previously treated with cumulative antraciclines doses and mediastinal radiotherapy. With a median follow up of 15 months progression free survival (PFS) is 79% and overall survival is 83%. 4/14 pts before Z-BEAM showed a subsequent progression and 2/15 relapsed: five pts died of lymphoma. No toxic deaths were recorded. In this group of pts with high risk relapsed/resistant NHL Z-BEAM+ASCT is able to achieve a good response with engraftment and toxicity not different from standard BEAM. This approach needs to be tested in a larger multicenter study. A matched pair analysis to compare this group with a similar group treated with standard BEAM without Zevalin is actually planned in our institution Disclosures: No relevant conflicts of interest to declare.

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