Intensive, Very Short-Term Chemotherapy for Advanced Burkitt’s Lymphoma in Children

2002 ◽  
Vol 20 (12) ◽  
pp. 2783-2788 ◽  
Author(s):  
Filippo Spreafico ◽  
Maura Massimino ◽  
Roberto Luksch ◽  
Michela Casanova ◽  
Graziella S. Cefalo ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
Short Term ◽  
Free Survival ◽  
Infusion Regimen ◽  
Disease Free

PURPOSE: To improve the 63% event-free survival (EFS) achieved before 1986 in Murphy’s stage III to IV Burkitt’s lymphoma (BL), both chemotherapy and supportive care were intensified. PATIENTS AND METHODS: From May 1987 to February 2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL were enrolled onto two sequential institutional studies. From 1987 to 1992, 30 patients were stratified according to the absence (regimen IA, n = 19) or presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5-week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients have been placed on regimen II, which is identical to IB but without ifosfamide. The scheduled duration of regimen II was 45 days. RESULTS: EFS and disease-free survival at 5 years are 81% ± 5% and 87% ± 5%, respectively, for 59 assessable patients (73% ± 8% and 85% ± 7% for regimen IA + IB, 89% ± 6%, EFS and disease-free survival, for regimen II; median follow-up, 6.7 years; range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II, died as a result of initial treatment failure or relapse, and five patients, none receiving regimen II, died as a result of treatment-related complications. CONCLUSION: This 45-day intensive chemotherapy program is the shortest schedule for disseminated BL and overcomes previously recognized risk factors such as BM and CNS infiltration.

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Dose Regimen ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Regimen ◽  
Disease Free

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

Evaluation of intensive postremission chemotherapy for adults with acute nonlymphocytic leukemia using high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide.

1987 ◽  
Vol 5 (6) ◽  
pp. 918-926 ◽  
Author(s):  
M S Tallman ◽  
F R Appelbaum ◽  
D Amos ◽  
R S Goldberg ◽  
R B Livingston ◽  
...  
Keyword(s):  
Cytosine Arabinoside ◽  
Disease Free Survival ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Survival ◽  
Kaplan Meier ◽  
To Receive ◽  
Disease Free ◽  
Historical Controls

In order to test the toxicity and efficacy of intensive postremission therapy with high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide in adults with acute nonlymphocytic leukemia (ANL), 100 adults (ages 19 to 75) with previously untreated ANL were entered into a study using six sequential cycles of chemotherapy. Cycles 1 (induction), 3, and 5 included conventional doses of daunomycin, cytosine arabinoside, 6-thioguanine, vincristine (VCR), and prednisone. Cycle 2 was cytosine arabinoside 3 g/m2 intravenously (IV) every 12 hours for four doses, followed by L-asparaginase 10,000 U intramuscularly (IM) at hour 42; this combination was repeated 1 week later. Cycle 4 included amsacrine 120 mg/m2/d and etoposide 100 mg/m2/d, both IV for five days, and cycle 6 was three monthly courses of VCR on day 1, and prednisone, mercaptopurine, and methotrexate each for five days. Seventy-four patients (74%) achieved complete remission (CR) (51 with cycle 1 and 23 after cycle 2). The overall disease-free survival (DFS) for patients achieving CR is 27% at 3 years by Kaplan-Meier analysis, while for patients achieving CR with cycle 1 it is 34%. The actuarial probability of being free from relapse at 3 years for patients achieving CR is 34%. Sixteen of the 74 CR patients (22%) died in CR while continuing to receive intensive chemotherapy, including 12 (18%) who succumbed to infection (nine bacterial, three fungal). After a median follow-up of 20 months, 36 patients have relapsed and 21 remain alive in CR. Intensive consolidation with high-dose cytosine arabinoside, amsacrine, and etoposide can modestly prolong DFS compared with historical controls. However, relapse continued to be a major problem and, in addition, with more aggressive consolidation therapy, infection during marrow aplasia resulted in a significant number of deaths.

Age and Response after Autologous Stem Cell Transplantation (ASCT) Define a Group of Long-Term Event-Free Survivors among Patients (Pts) with Low-Grade Follicular Lymphoma (FL): A Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1883-1883
Author(s):  
Charalambos Andreadis ◽  
Elise A. Chong ◽  
Edward A. Stadtmauer ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Autologous Bone Marrow ◽  
Large Cell ◽  
High Dose ◽  
Low Grade ◽  
Free Survival ◽  
Disease Free

Abstract Introduction: FL is generally responsive to conventional-dose chemotherapy but long term disease-free survival (DFS) is uncommon. High-dose chemo-radiotherapy followed by ASCT has the potential to induce remission in this disease but the long-term benefit of this modality remains to be determined. Methods: Between 1990 and 2003, we transplanted 52 pts originally diagnosed with low-grade FL (31 grade 1, 21 grade 2). Twenty-five (48%) had biopsy-proven large cell transformation (FL grade 3 or diffuse large cell lymphoma) before ASCT. The median number of prior therapies was 2 (range: 1 to 7). Prior to ASCT, 45 pts (87%) were responsive to salvage therapy with 20 pts (38%) in CR. Five pts (10%) had chemo-resistant disease at the time of ASCT. High-dose regimens included BCNU-cyclophosphamide-etoposide (31%), melphalan/TBI (27%), and cyclophosphamide/TBI (25%). Thirty-eight pts (73%) received peripheral stem cells (PSCT) and 14 pts (27%) received autologous bone marrow (BM) with 4-hydroxyperoxycyclophosphamide (4-hc) purging in 9 cases (17%). The median age was 49 yrs (range: 29–65). Results: There was 1 treatment-related death during the first 100 days. After ASCT, 36 pts (69%) achieved a CR, 2 (4%) had a PR, and 7 (13%) had stable disease. Among those in CR, 20 (56%) had a CR pre-ASCT, 14 (41%) had a lesser response, and 1 (3%) was chemo-resistant. Median follow-up (f/u) of survivors was 5.3 yrs (range: 1.7 months to 12.4 yrs). The median overall survival (OS) has not yet been reached. The median event-free survival (EFS) is 3.4 yrs (range: 1.7 months to 12.4 yrs). Among complete responders, more than 50% are disease free at last follow-up (range 1.7 months to 12.1 yrs). Variables favorably affecting EFS and OS are age < 60 yrs (p = 0.007, 0.015 respectively), achievement of a CR after ASCT (p = 0.002, 0.001), absence of transformation (p = 0.038, 0.017), BM vs. PSCT (p = 0.042, 0.086), and 4-hc BM purging (p = 0.044, 0.059). Number of prior regimens, response prior to ASCT, type of preparative regimen, and addition of TBI, were not significantly associated with EFS, DFS, or OS. In multivariable analysis, achievement of CR after ASCT and age < 60 yrs are the only significant predictors of EFS and OS. Adjusted for age, 53% of pts with a CR after ASCT are alive and event-free at last f/u (range: 2.4 months to 12.4 yrs) (Figure 1). In contrast, the median EFS among pts without a CR is 0.5 yrs (range: 1.7 months to 5.3 yrs). Conclusion: ASCT is a reasonable therapeutic approach to FL, resulting in long term EFS for some pts, even with relapsed, refractory and/or transformed disease. In our experience, significant predictors of EFS and OS after ASCT are complete response and age <60. The appropriate application and timing of ASCT in the management of pts with FL needs to be further evaluated in randomized, controlled clinical trials. Figure Figure

Can High Dose Therapy Change the Course of Low Grade Lymphoma? A Study Considering Patients as Their Own Control.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1882-1882
Author(s):  
Stephane Vignot ◽  
Nicolas Mounier ◽  
Guillaume Sergent ◽  
Pauline Brice ◽  
Jean-Pierre Marolleau ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Tumor Burden ◽  
High Dose ◽  
Low Grade ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
New Strategy ◽  
Disease Free

Abstract Low grade lymphoma patients (pts) have an indolent evolution with median survival ranging between 8–10 years. During disease’s course, high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) can be considered as an alternative to sequential chemotherapies. However, efficacy of this strategy remains controversial. The purpose of our study is to evaluate ASCT efficacy by comparing retrospectively for each pts disease free survival (DFS) after ASCT with DFS observed with pts’ last chemotherapy regimen (LCR) just before intensification. Between apr 1988 and feb 2002, 109 low grade lymphoma pts were treated with HDT and ASCT in our department, 61 were male, the median age was 49 yrs [range 28–65]. Histological subtypes were mostly follicular small cell (86 %). At time of diagnosis, LDH were normal for 85 pts; 60 pts had high tumor burden. IPI was 0 for 16 %, 1 for 70 % and 2 for 14 %. Prior to ASCT, pts had experienced a median of 2 progressions (range 1 to 5). At time of graft, 102 pts present complete or partial response and 7 pts present stable disease. Two principal intensification chemo regimens were used before ASCT: VP16/cyclophosphamide in 84 pts and BEAM in 12. TBI was associated for 86 pts. At June 2002, the median follow up was 6.4 yrs from diagnosis and 4.5 yrs from ASCT. 3 years after ASCT, survival rate was 72 % and DFS rate was 50 %. Median DFS decreased with nb of progression (p=0.02): Median DFS according to nb of progression Nb of progression 1 2 3 > 3 Nb pts (%) 17 (16) 57 (52) 28 (26) 7 (6) Median DFS in yrs 6.4 5.1 1.8 1.0 Considering pt with more than 1 progression (n=92) as his own control, DFS was longer after ASCT than after LCR for 61 % of pts. Median DFS was 2.5 yrs after ASCT and 2.0 yrs after LCR. At 3 yrs, DFS rate was 48 % after ASCT and 37 % after LCR (p<0,001): Figure Figure This study demonstrates that HDT and ASCT significantly increase DFS in comparison with the LCR for low grade lymphoma patients. Such methodology could be useful to evaluate new strategy incorporating monoclonal antibody.

Autologous Transplantation in De Novo Non-Promyelocytic Acute Myeloid Leukemia (AML) Patients in First Complete Remission (CR1) with Peripheral Blood Stem Cell (PBSC) Collection Following Consolidation with High-Dose Cytarabine and Etoposide: A Single Institution Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4461-4461
Author(s):  
Eugene Choi ◽  
Lingyi Chen ◽  
Srikanth Nagalla ◽  
Vamshi Kaveti ◽  
Regina Mullaney ◽  
...  
Keyword(s):  
De Novo ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Kaplan Meier ◽  
Cd34 Cells ◽  
High Dose Cytarabine ◽  
Lost To Follow Up ◽  
Disease Free

Abstract INTRODUCTION: Autologous PBSC transplant is an important yet evolving treatment modality for patients with AML. However, the ideal mobilization regimen from which to collect PBSC remains in question. Previous reports have indicated that highdose cytarabine with etoposide is both safe and effective in terms of successful PBSC procurement, subsequent engraftment, and disease outcome. METHODS: At our institution from 1994 to 2007, 38 consecutive patients with de novo non-promyelocytic AML in first complete remission following conventional induction chemotherapy were consolidated with high-dose cytarabine (2000mg/m2 IV q12h × 8 doses, days 1–4) and etoposide (40mg/kg IV over 96h) followed by G-CSF 5 mg/kg subcutaneously starting d14 until completion of PBSC collection. Patients underwent myeloablative therapy with busulfan (1mg/kg po q6h × 16 doses, days –7 to -4) and etoposide (60 mg/kg IV over 10h, day -3) with PBSC infusion occurring on day 0 with daily G-CSF 5 mg/kg. Data regarding stem cell yield, engraftment and patient outcome was collected retrospectively. RESULTS: The average patient age was 44 years (range 19–70). Following consolidation, at least 2×106 CD34 cells/kg were isolated from all 38 patients with a median of 9.4×106 (range 2.2–43) CD34 cells/kg over a mean of 4 collections (range 1–11). Overall, 36 of 38 (95%) remained in CR and went onto PBSC transplant (one died from infectious complications during consolidation, one relapsed before transplant). The median number of stem cells infused was 8.8×106 CD 34 cells/kg (range 2.2–47). All 36 patients engrafted with the mean number of days to neutrophil recovery (ANC&gt;500) being 11 (range 8–17) and the mean number of days to platelet recovery (&gt;20,000) being 12 (range 8–19). Disease-free outcomes in patients undergoing PBSC transplant while in CR1 are presented in Figure 1. The 3y overall survival in all pts was 66%, and 56% at 5y. For good-risk cytogenetic patients, 3y OS was 78% and the 5y OS was 75%. For intermediate-risk cytogenetic patients, OS was 47% and 36% at 3y and 5y respectively. Three patients with poor cytogenetics were autulogously transplanted. One patient relapsed at day 111 and expired at day 450. The second patient remains in CR at day 246. The third patient relapsed at day 104 and expired at day 322. CONCLUSION: In patients with de novo non-promyelocytic AML in CR1, consolidation with high-dose cytarabine plus etoposide is safe and provides excellent yield of PBSCs upon growth factor accelerated hematological recovery. Subsequent engraftment after autologous transplanation is rapid. Our outcomes support the viability of this regimen in patients with good and intermediate-risk cytogenetics. Figure 1: Kaplan-Meier analysis of disease-free survival following autologous PBSC transplant. Cytogenetic analysis was unavailable in 5 patients, and 1 patient was lost to follow-up. Figure 1:. Kaplan-Meier analysis of disease-free survival following autologous PBSC transplant. Cytogenetic analysis was unavailable in 5 patients, and 1 patient was lost to follow-up.

90Y-Ibritumomab Tiuxetan (Zevalin®) in Combination with High-Dose Therapy (HDT) Followed by Autologous Stem Cell Transplant (ASCT) May Improve Survival in Patients with Poor-Risk Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL): Results of a Retrospective Comparative Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 327-327 ◽  
Author(s):  
Auayporn P. Nademanee ◽  
Amrita Krishnan ◽  
Nicole Tsai ◽  
Joycelynne Palmer ◽  
Arturo Molina ◽  
...  
Keyword(s):  
B Cell ◽  
Performance Status ◽  
Disease Free Survival ◽  
Disease Status ◽  
High Dose ◽  
Free Survival ◽  
Poor Risk ◽  
Disease Free

Abstract Since NHL is radiosensitive, total body irradiation (TBI) has been used as part of HDT and ASCT for NHL. However, due to short-term and long-term toxicity associated with TBI, alternative regimens have been developed. We have reported that Zevalin at conventional and high doses can be given in combination with HDT and ASCT in patients (pts) with poor-risk or relapsed B-cell NHL without additional toxicity. Given the efficacy of Zevalin in FL and DLBCL, we retrospectively evaluated the outcome of HDT and ASCT in pts with FL and DLBCL who received Zevalin-based HDT regimens (Z-ASCT) and compared to those receiving TBI-based regimen (TBI-ASCT)Between 1/2000 to 1/2006, 187 pts with FL grade I/II (30), FL grade III (20) and DLBCL (137) underwent HDT and ASCT, 62 received Z-ASCT while 125 received TBI-ASCT. For Z-ASCT, pts < 60 years old without prior radiotherapy (RT) received high-dose Zevalin in combination with high-dose etoposide and cyclophosphamide while pt > 60 yrs or with prior RT received conventional dose Zevalin plus high-dose BEAM. TBI-ASCT was performed during the same period for the following reasons: ineligible for Z-ASCT, pt refusal, physician preference and protocol closure. The pt characteristics between the two groups were similar with respect to histology, disease status, prior regimens, bulky disease, B symptoms and performance status. However, the median age was younger for TBI-ASCT (49 vs. 53, p=0.01) and there were more chemo-resistant pts in the Z-ASCT group (p=0.01). Results: At a median follow-up of 28 months (range 2–64) for Z-ASCT and 38 months (range 1–78) for TBI-ASCT, the 2-year overall survival (OS) and disease-free survival (DFS) were 91% (95% CI, 82–96) and 74% (95% CI, 64–82), respectively for Z-ASCT, and 76% (95% CI, 69–80) and 72% (95% CI, 65–77), respectively for TBI-ASCT(Figure 1). OS remained significantly different when first complete remission pts were excluded from analysis (p=0.019). Multivariate models were generated for the primary endpoints of the study (OS and DFS). The results of these analyses showed that the risk of death and/or relapse was less among the Z-ASCT pts after adjusting for baseline differences (ie. Age, performance status and chemosensitivity status at transplant), and other factors (i.e., disease status at transplant, number of previous chemotherapies) previously shown to be associated with survival/disease free survival post transplant (OS: p<0.01 | DFS: p<0.10). Conclusion: Zevalin in combination with HDT followed by ASCT was associated with significantly improved survival in pts with poor-risk or relapsed/refractory FL and DLCBL when compared to TBI-ASCT. Further studies and longer follow-up are required to evaluate the long-term efficacy and safety of Zevalin in the HDT/ASCT setting. Figure Figure

Ten Year Follow up Analysis of the OSHO Phase III Trial (AML 96) Comparing Different Application Modes of AraC in Patients below 60 Years with Acute Myeloid Leukemia (AML): No Impact of AraCApplication Mode on Remission Rate, Toxicity, Disease-Free Survival or Overall Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2966-2966
Author(s):  
Cornelia Becker ◽  
Rainer Krahl ◽  
Antje Schulze ◽  
Georg Maschmeyer ◽  
Christian Junghanß ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Significant Difference

Abstract Clinical trials on different cytarabine doses for treatment of AML provide evidence of a dose response effect, but also for increase toxicity after high dose AraC (HDAC). Pharmacokinetic measurements of cytarabine-triphosphate (AraC-CTP), which is the most relevant cytotoxic metabolite of AraC, have revealed its formation in leukemic cells to be saturated with infusion rates above 250 mg/m2/h, this being significantly lower than used in HDAC schedules. Methods: Based on a pharmacological model and encouraging results of a phase II study we conducted a prospective randomized multicenter clinical trial comparing the effects of two different application modes of AraC in patients up to 60 years with untreated newly diagnosed AML. Patients were randomized to receive AraC at two different infusion rates (IR) during induction and consolidation treatment: arm A/experimental: 1 × 2 g/m2/d AraC over 8 hours (IR 250 mg/m2/h) arm B/standard: 2 × 1 g/m2/d AraC over 3 hours (IR 333 mg/m2/h). Induction and first consolidation consisted of AraC (days 1, 3, 5, 7) in combination with an anthracycline (Idarubicine 12 mg/m2 or Mitoxantrone 10 mg/m2, days 1–3). The final dosage points (AraC day 7 and anthracycline day 3) were excluded from the second consolidation. The third consolidation consisted of either allogeneic or autologous stem cell transplantation or of chemotherapy identical to second consolidation. Results: From 02/97 to 04/02 419 patients were enrolled in the study. The present analysis is based on 361 eligible and evaluable patients with a median follow up of 7 years. CR was reached in 249/361 (69%; 95%CI: 65%–74%) patients. No statistically significant differences were detected between arms A and B with regard to CR-rate (69% vs 69%) or early death rate (11% vs 8%). Hematological recovery of median white blood cell count (WBC) &gt; 109/l and median platelets (plt) &gt; 50 × 109/l revealed no difference between arms A and B after induction (WBC day 22 vs 22, p=0,68; plt day 25 vs 26, p=0,41) and consolidation (WBC day 28 vs 27, p=0,07; plt day 42 vs 40, p= 0,58). The event free survival (EFS) after 5 years is 0,25 ± 0,03 % for all patients with an overall survival of 0,31 ± 0,03 % after 5 years. For the purposes of analysis, the 83 transplant patients (23 allogeneic MRD, 14 allogeneic MUD and 46 autologous) were censored at time of transplant. No statistically significant difference between arms A and B in regard to EFS (0,25 ± 0,04 vs 0,25 ± 0,04, p=0,99), relapse incidence (0,63 ± 0,06 vs 0,60 ± 0,06, p=0,89), overall survival (0,32 ± 0,04 vs 0,30 ± 0,04, p=0,44) and therapy associated mortality (0,18 ± 0,04 vs 0,17 ± 0,03, p=0,95) were detectable after adjustment of prognostic factors. An analysis of risk factors by multivariate cox regression model confirmed cytogenetics at diagnosis to be the most important risk factor for CR rate (p&lt;10−6) and for EFS (p&lt;10−6). Other significant prognostic factors for EFS evaluated in the multivariate analysis were de novo vs secondary AML (p=0,0001), WBC (continuous) (p=0,001), LDH (&gt;1–4 × vs other ULN) (p=0,008) and FAB classification (FAB M0,6,7 vs FAB M1,2,4,5) (p=0,0005). EFS after 5 years shows a significant correlation to cytogenetics (p&lt;10−6) with 0,71±0,1, 0,27±0,05, 0,20±0,06 and 0,03±0,03 for favorable, normal, other and unfavorable cytogenetic karyotype, respectively. Conclusion: We conclude that the application of AraC at the presumptive saturating infusion rate of 250 mg/m2/h results in comparable remission rates, toxicity, event free survival and overall survival as compared to the standard IR with 333 mg/m2/h.

Minimizing Therapy for Patients with Acute Promyelocytic Leukemia: Efficacy of Single Cycle of Arsenic-Based Consolidation Therapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1932-1932
Author(s):  
Steven D. Gore ◽  
Lawrence Morris ◽  
Ivana Gojo ◽  
Marcel P. Devetten ◽  
Katarzyna Jamieson ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Event Free Survival ◽  
Rt Pcr ◽  
Single Cycle ◽  
Free Survival ◽  
Disease Free

Abstract Current strategies for the treatment of patients with acute promyelocytic leukemia provide event-free survival of 75 – 85%. Most multicenter studies have used large doses of anthracyclines and multiple cycles of treatment. Based on the extremely high efficacy of arsenic trioxide (ATO) as single agent re-induction therapy, we conducted a Phase II study which minimized anthracycline exposure and treatment duration in newly diagnosed APL patients. The study design was modified from a previous trial which successfully used a single cycle of consolidation chemotherapy (Am. J. Heme.2005;79:119–27). All patients received ATRA for 60 days with daunorubicin (DRN, 60 mg/m2/dose IV) on days 4, 6, 8 unless urgent cytoreduction was required. Consolidation, begun between days 60 and 67, consisted of cytarabine 0.667 gm/m2/day IV continuous infusion days 1 – 3, DRN 60 mg/m2/dose IV days 1 – 3, and ATO 0.15 mg/kg IV for 30 doses, administered five days per week beginning on day 8 of consolidation on an outpatient basis. A second module of ATO was planned for patients with a positive qualitative rt-PCR for PML-RARα (sensitivity 1/10000) following recovery from consolidation. Patients whose initial WBC was &lt; 10,000 per microliter proceeded to ATRA maintenance given for 15 days every three months for 8 cycles. Patients with WBC counts greater than 10,000 per microliter also received 6-mercaptopurine and methotrexate as part of the maintenance regimen. Forty-five patients received induction therapy. Median age was 50; relapse risk categories (Sanz et al. Blood. 2000;96:1247–1253): Low, 36%; Intermediate, 29%; High, 32%. Four patients expired during induction. Of the 41 remaining patients, 4 patients withdrew consent prior to consolidation due to difficulty traveling to the treatment center. 27/31 patients tested following induction achieved molecular remission at that time point (qualitative rt-PCR). 37 patients received consolidation therapy. No patients expired during consolidation, and no patients required a second module of ATO therapy. Only two events have been recorded in patients who underwent consolidation treatment: one patient with Hemoglobin SC disease expired during maintenance therapy due to intrahepatic sickle crisis, possibly related to methotrexate administration, while one patient developed central nervous system relapse. The table compares overall, event free- and disease-free survival of this series to three recent series, including the ATO-containing arm of C9810. Although median follow-up of the current series is shorter, to date the results are comparable to these three studies which employed more extensive therapy. No cases of secondary MDS or AML have been reported to date. Echocardiographic monitoring pre- and post-induction therapy in 24 patients revealed a decrement in ejection fraction post-induction of ≥ 10% in nine patients, including &gt; 20% in three patients to EF values of 20 – 30%, with biopsyproven anthracycline-induced cardiomyopathy documented by biopsy in two patients, indicating possible cardiac sensitization by ATRA to anthracycline. These data suggest that the inclusion of ATO in primary APL management may allow further minimization of conventional cytotoxic chemotherapy without compromising cure rates, and demonstrate the critical need to determine the minimum curative therapy for APL patients. Series Total anthracycline dose administered (mg/m2 DRN equivalent)a Age (median) Sanz Relapse risk: High (percent) Follow- up (years, median) Overall survival Disease- Free Survival Event- Free Survival a Daunorubicin= 1. Mitoxantrone = 2.5. Idarubicin = 5. b nr indicates not reported c Selected based on Sanz risk score 90.5 92.9 83.6 Current 360 50 32 1.8 86 87 77 C9710 ATO arm 500 nrb 24 2.4 82 84 nr PETHEMA LPA99 525 – 625c 37 25 5.4 APL2000 Ara-C arm 495 43 46 5.2 90.5 nr 85.6

High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin's disease and non-Hodgkin's lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells.

1994 ◽  
Vol 12 (10) ◽  
pp. 2176-2186 ◽  
Author(s):  
A Nademanee ◽  
I Sniecinski ◽  
G M Schmidt ◽  
A C Dagis ◽  
M R O'Donnell ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Disease Free Survival ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
Hematopoietic Recovery ◽  
Stimulating Factor ◽  
Disease Free

PURPOSE To evaluate (1) the effect of granulocyte colony-stimulating factor (G-CSF) on peripheral-blood stem-cell (PBSC) mobilization; (2) the rate of hematopoietic recovery after G-CSF-mobilized PBSC transplantation; and (3) the outcome of high-dose myeloablative therapy and PBSC transplantation in patients with relapsed or refractory lymphoma. PATIENTS AND METHODS Ninety-five patients with lymphoma underwent high-dose therapy followed by PBSC transplant in three sequentially treated cohorts of patients in a nonrandomized study. The first 30 patients received nonmobilized PBSCs (unprimed) without G-CSF after transplant, the next 26 patients received PBSC that were mobilized with G-CSF 5 micrograms/kg/d (primed-5) plus G-CSF after transplant, and the last 39 patients received PBSC mobilized by G-CSF 10 micrograms/kg/d (primed-10) plus G-CSF after transplant. The conditioning regimen consisted of fractionated total-body irradiation (FTBI) 12 Gy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg. Patients with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. RESULTS The use of G-CSF-mobilized PBSCs in combination with G-CSF posttransplant resulted in a significantly accelerated time to recovery of both granulocyte and platelet when compared with the unprimed group. The median number of days to an absolute granulocyte count (ANC) of greater than 0.5 x 10(9)/L was 10 days for G-CSF primed versus 20 days for the unprimed (P = .0001). The median days to platelet transfusion independence was 16 and 31 days (P = .0001) for the G-CSF primed and unprimed, respectively. There were also significant reductions in the number of platelet (P = .02) and RBC transfusions (P = .006) for the G-CSF primed. Multivariate analysis of prognostic factors identified CD34+ cell dose as the only additional factor predicting engraftment. Sixty-nine patients are alive at a median follow-up of 15.9 months (range, 7.4 to 63.7). The cumulative probability of 2-year disease-free survival is 59% (95% confidence interval [CI], 36% to 79%) and 39% (95% CI 25% to 55%) for patients with Hodgkin's disease and non-Hodgkin's lymphoma, respectively. CONCLUSION The use of G-CSF-mobilized PBSC after high-dose myeloablative therapy resulted in a rapid, complete, and sustained hematopoietic recovery. Disease-free survival over 2 years can be achieved in some patients with relapsed lymphoma after high-dose therapy and PBSC transplantation. However, longer follow-up is required to confirm the curability of this approach.

Is Rituximab Needed With High Dose Chemotherapy and Autologous Stem Cell Transplant When Patients With Non-Hodgkin’s Lymphoma Have Been Exposed To It?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5552-5552
Author(s):  
Zartash Gul ◽  
Stephan Anderson ◽  
Stacey Slone ◽  
Saurabh Chhabra ◽  
Gregory Monohan ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Disease Free

Abstract Introduction The value of Rituximab with High dose chemotherapy and autologous stem cell transplant (auto-HCT) has been evaluated in some retrospective studies. It is noted that the addition Rituximab to auto-HCT results in significant improvement in overall (OS) and disease free survival (DFS). However, it is unclear that the addition of Rituximab with auto-HCT would result in significant benefit in patients who have received prior Rituximab based therapy. Methods We retrospectively evaluated twenty seven consecutive patients who had B cell non-Hodgkin's lymphoma (NHL) and underwent auto- HCT at Markey cancer center between January 2010 and December 2012. All patients received 375 mg/m2of Rituximab with chemotherapy. Rituximab was not administered with high dose chemotherapy (BEAM: BCNU, Etoposide, Cytarabine and Melphalan) prior to auto-HCT. All patients received GCSF starting day 5 after auto-HCT. Results There were 27 patients who underwent auto-HCT for NHL. Median age of the patients was 60 years (36-72 years). Nineteen patients were male and 8 patients were female. Fifteen patients were in complete remission (CR) and the rest were in partial remission (PR). Patients had: Diffuse large B cell lymphoma (DLBCL=11 patients): Mantle cell lymphoma (MCL=13 patients): follicular lymphoma (3 patients). Median CD 34 count of infused cells was 4.14 x 106 cell/kg (2.26- 9.45). Median time to neutrophil recovery was 11 days (9-14). Median lymphocyte count at day 30 after auto HCT was 1130 x 10 6/l (320- 5180). After a median follow up of 7.9 months (3.0- 32.4) eight patients had relapsed. Five patients who had relapsed had refractory disease before auto-HCT. Non -Relapse mortality (NRM) is shown in figure 1. Median overall survival and disease free survival were not reached. Seventy percent patients had not relapsed. We did not find any factors associated with relapse. Conclusion We performed a retrospective study to evaluate the impact of Rituximab with high dose chemotherapy and in patients with NHL. Review of literature showed that median 2 year and 5 year OS was 80% and 69% in patients who received Rituximab with auto HCT. Median 2 year DFS was 67%. In our study 70% patients were relapse free at a median follow up of 8 months. We would need a longer follow up to determine the efficacy of Rituximab with auto- HCT in patients with NHL who had prior exposure to Rituximab. Disclosures: Off Label Use: The use of Thymoglobulin® for GVHD prevention. Hayslip:Sanofi: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Celgene: Research Funding.

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