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 ◽  
...  

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.

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1407-1411 ◽  
Author(s):  
SN Wolff ◽  
J Marion ◽  
RS Stein ◽  
JM Flexner ◽  
HM Lazarus ◽  
...  

Abstract High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4461-4461
Author(s):  
Eugene Choi ◽  
Lingyi Chen ◽  
Srikanth Nagalla ◽  
Vamshi Kaveti ◽  
Regina Mullaney ◽  
...  

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>500) being 11 (range 8–17) and the mean number of days to platelet recovery (>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.


2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.


Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1144-1147
Author(s):  
BA Peterson ◽  
CD Bloomfield

Twenty-six of 45 adults (58%) with acute nonlymphocytic leukemia who were treated with intensive induction chemotherapy over 5 yr ago entered complete remission. All patients entering remission were placed on weekly maintenance chemotherapy consisting of cytosine arabinoside and 6-thioguanine. The median duration of complete remission was 17 mo and 7 patients (27%) remained in their initial remission for 62 + to 102 + mo. All but one of the patients in complete remission over 5 yr have had treatment discontinued. Only 1 of 7 patients in remission for more than 5 yr has relapsed. Median survival is 26.5 mo, and 8 patients (31%) currently remain alive without evidence of leukemia 63--105 mo from diagnosis. It is possible to achieve long-term disease-free survival with chemotherapy alone in acute nonlymphocytic leukemia.


2010 ◽  
Vol 76 (7) ◽  
pp. 675-681 ◽  
Author(s):  
Matthew R. Bower ◽  
Charles R. Scoggins ◽  
Robert C. G. Martin ◽  
Michael P. Mays ◽  
Michael J. Edwards ◽  
...  

The objective of this study was to determine the incidence of multiple primary melanomas (MPM) and other cancers types among patients with melanoma. Factors associated with development of MPM were assessed in a post hoc analysis of the database from a multi-institutional prospective randomized trial of patients with melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis. Forty-eight (1.9%) of 2506 patients with melanoma developed additional primary melanomas. Median follow-up was 66 months. Except in one patient, the subsequent melanomas were thinner (median, 0.32 mm vs 1.50 mm; P < 0.0001). Compared with patients without MPM, patients with MPM were more likely to be older (median age, 54.5 vs 51.0 years; P = 0.048), to have superficially spreading melanomas (SSM) ( P = 0.025), to have negative sentinel lymph nodes ( P = 0.021), or to lack lymphovascular invasion (LVI) ( P = 0.008) with the initial tumor. On multivariate analysis, age ( P = 0.028), LVI ( P = 0.010), and SSM subtype of the original melanoma ( P = 0.024) were associated with MPM. Patients with MPM and patients with single primary melanoma had similar DFS (5-year DFS 88.7 vs 81.3%, P = 0.380), but patients with MPM had better OS (5-year OS 95.3 vs 80.0%, P = 0.005). Nonmelanoma malignancies occurred in 152 patients (6.1%). Ongoing surveillance of patients with melanoma is important given that a significant number will develop additional melanoma and nonmelanoma tumors. With close follow-up, second primary melanomas are usually detected at an early stage.


2005 ◽  
Vol 23 (27) ◽  
pp. 6730-6738 ◽  
Author(s):  
Joseph Wee ◽  
Eng Huat Tan ◽  
Bee Choo Tai ◽  
Hwee Bee Wong ◽  
Swan Swan Leong ◽  
...  

Purpose The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. Patients and Methods Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. Results Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). Conclusion This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.


1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  

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.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1883-1883
Author(s):  
Charalambos Andreadis ◽  
Elise A. Chong ◽  
Edward A. Stadtmauer ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  

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


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1882-1882
Author(s):  
Stephane Vignot ◽  
Nicolas Mounier ◽  
Guillaume Sergent ◽  
Pauline Brice ◽  
Jean-Pierre Marolleau ◽  
...  

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.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10725-10725 ◽  
Author(s):  
F. Moura Silva ◽  
C. Tosello ◽  
M. T. Laloni ◽  
C. M. Andrade ◽  
A. Bertozzi ◽  
...  

10725 Background: To evaluate the efficacy of the Epirubicin as a part of the FEC60 AdCT in operable BrC patients in a Brazilian single-center. Methods: We verified retrospectively our experience with FEC 60 as AdCT in pre and postmenopausal, node positive and negative, pathologic stage I, II and III patients with BrC. Pts were submitted after surgery to receive Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 every 28 days for 6 cycles. Pts who were ER+ and/or PR+ received Tamoxifen (TMX) 20 mg/day for 5 years after AdCT. Radiotherapy was also offered at the end of AdCT if indicated. All patients were evaluated in terms of 10 year (y) Disease Free Survival (DFS) and Overall Survival (OS). The most common toxicities (acute and chronic) and metastatic sites will also be reported. Results: Between July 1983 and December 1995 a total of 752 patients (ranging from 22 to 77 years old - median 47.7) were encountered and all of them were evaluated to 10 year (y) DFS and OS. Approximately 61% of these patients received adjuvant TMX. Pts in premenopausal and postmenopausal represented 62.5% and 37.5% respectively. 72 (11%) pts had pathological stage I; 353 (46%) pts had stage II and 327 (43%) had stage III. The 10y DFS was 70%, 46% and 19% for stage I, II and III respectively. The 10y OS after a minimal follow-up of 122.98 months was 74%, 48% and 20% for stage I, II and III respectively. Conclusions: Our results demonstrated that FEC 60 regimen is active and well tolerated in the adjuvant treatment for BrC pts. We had about 89% of stage II and III pts and in this population FEC60 regimen add benefit. Nevertheless, the randomized studies indicate that the greatest anticancer effect of Epirubicin requires doses ranging from 75 to 120 mg/m2, but due to economic reasons (we integrate the brazilian public healthy system) we could not offer dosages greater than 60 mg/m2. FEC 60 was feasible and offered reasonable results in our population in terms of 10y DFS and OS. No significant financial relationships to disclose.


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