scholarly journals Long-term disease-free survival in acute nonlymphocytic leukemia

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.

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

Abstract 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.


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 ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Norio Asou ◽  
Yuji Kishimoto ◽  
Hitoshi Kiyoi ◽  
Masaya Okada ◽  
Yasukazu Kawai ◽  
...  

To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RARα at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P = .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RARα fusion transcript after 3 courses of intensive consolidation therapy.


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 ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1030-1030
Author(s):  
Lucy A Godley ◽  
Uchenna O. Njiaju ◽  
Margaret Green ◽  
Howard Weiner ◽  
Shang Lin ◽  
...  

Abstract Abstract 1030 Poster Board I-52 Few clinical protocols have focused exclusively on the care of patients with therapy-related myeloid neoplasms (t-MN), and typically the disease confers a poor prognosis. We conducted a clinical trial exclusively for these patients. Between February 2003 and February 2009, we enrolled 32 adult patients with untreated t-MN. The median age was 56 years old (range, 23-83), and 38% were >60 years old. Eight patients (25%) had a total combined Charlson comorbidity index of >4, indicating that they were at high-risk for toxicity from the treatment, either due to older age or medical co-morbidities. T-MN developed following cytotoxic therapy for a malignant disease in 28 patients (88%), following cytotoxic therapy for rheumatologic disease in 2 patients (6%), and with immunosuppressive therapy after solid organ transplants in 2 patients (6%). The latency interval was highly variable, but the greatest fraction of patients (28%) experienced a latency of 4 - 9 years between their primary cytotoxic treatment and development of t-MN (median latency, 3.6 years; range 0.9-23 years). In 8 patients (25%), the latency was 2 years or less. 84% of patients had clonal cytogenetic abnormalities; 35% had a complex karyotype; 45% had abnormalities of chromosomes 5 or 7 or both.; 5 patients had t(9;11). All patients received induction chemotherapy with high-dose cytarabine (3,000mg/m2 over 4 hours) followed immediately by mitoxantrone (30mg/m2 over 1 hour), both given once on days 1 and 5 in a timed-sequential schedule. The complete remission (CR) rate after a single course was 66% and the partial remission (PR) rate was 16%, for an overall response rate of 82%. Grade 4 cardiac dysfunction occurred in 4 patients, resulting in the early death of one. Three of these patients had normal ejection fractions prior to beginning induction chemotherapy (including the patient who died), and one began therapy with an ejection fraction of 43%. Among the 21 patients who achieved a CR, 13 (62%) received consolidation therapy with allogeneic HCT, 4 (19%) received an autologous HCT, and 3 (14%) received only further chemotherapy. Three of the 5 patients who achieved a PR received an allogeneic HCT. Long-term disease-free survival (DFS) was observed in patients with each of the 3 modalities of consolidation therapy. The median overall survival (OS) was 399 days (range, 15-1972+), and OS at 1 year was 51%. Survival was significantly better among those patients who achieved a CR (median, 673 days) compared to those who had a PR (median, 126 days) to induction chemotherapy (P=0.003). OS at 1 year was 74% for patients who had achieved a CR compared with 20% for patients who had achieved a PR to induction. Median DFS was 415 days, with 59% of patients remaining disease-free at 1 year. OS was significantly longer in patients who underwent HCT compared to those who did not. The median survival for patients who received an allogeneic HCT was 673 days (range, 74-1798+) compared to 399 days for patients who received an autologous HCT (range, 353-917+), and 93 days for patients who received no transplant (range, 15-1972+) (P=0.002). OS at 1 year was 72% for patients who had undergone an allogeneic HCT, 75% for patients who had an autologous HCT, and 17% for patients who had not received a transplant. The DFS at 1 year was 67% for patients who underwent either an allogeneic or autologous stem cell transplant compared to 25% for those who did not have a transplant. To date, 9 patients (28%) remain alive and disease-free: 7 (22%) after allogeneic HCT; 1 after autologous HCT; and 1 after consolidation with only chemotherapy. Overall, remission induction therapy with high-dose cytarabine and mitoxantrone is an effective and tolerable regimen for patients with t-MN, allowing aggressive consolidation regimens, HCT, and long-term disease-free survival. Disclosures: Stock: Genzyme: Research Funding.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9069-9069
Author(s):  
A. A. Patel ◽  
P. M. Shah ◽  
K. M. Patel ◽  
S. N. Shukla ◽  
B. J. Parikh ◽  
...  

9069 Background: Pediatric nasopharyngeal carcinoma (PNC) represents a locally advanced undifferentiated tumor. In this study, clinical experience and therapeutic results of 24 children with newly diagnosed PNC, treated in a single oncology institution in India over a period of 5 years, are analyzed. Methods: 24 patients (23 males and 1 female) 7–14 years old (median = 12) from Jan 2000 to Sep 2005 with PNC were retrospectively evaluated. 18/24 patients were evaluable. 16 patients received induction chemotherapy followed by radiotherapy while 1 patient was offered concurrent chemoradiotherapy, 1 patient received radiotherapy alone. 15/16 patients received postradiation chemotherapy. The agents used in induction and adjuvant therapy were cisplatin (100 mg/m2) on day 1 and 5-fluorouracil 750 mg/m2 for 5 days. The dose of radiotherapy used was 60 gray in 30 fractions. Results: The time of onset of symptoms to diagnosis ranged from 1 month to 9 months with a median of 5.5 months. Histopathology was lymphoepithelioma in 5 patients (27.7%) while 13 patients (72.2%) had poorly differentiated carcinoma. Disease extent was T2 (n = 7), T3 (n = 6), and T4 (n = 5); N1 (n = 5), N2 (n = 7), and N3 (n = 5). 7 patients had intracranial invasion. None had metastatic disease on presentation. 13 patients (72.2%) achieved major response which included 7 (38.8%) complete remission and 6 (33.3%) partial remission after the induction chemotherapy and radiotherapy. 4 (22.2%) had progressive disease. Another 3 (16.6%) attained complete remission after post radiation chemotherapy which consisted of two cycles of cisplatin and 5-flourouracil. The follow up ranged from 5 months to 84 months with a median follow up of 35 months. The disease free survival ranged from 10 months to 53 months with a median of 33 months. The patients who had a better response to induction chemotherapy had a better disease free survival. Out of 7 patients who attained complete remission 2 relapsed with a median time to first relapse of 9.5 months. Toxicity to therapy was modest. Only one patient had grade 4 neutropenia and mucositis. There was no therapy related mortality. Conclusion: Chemoradiotherapy for nasopharyngeal carcinoma in children is an effective treatment modality with minimal toxicity. No significant financial relationships to disclose.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2805-2805
Author(s):  
Olga A. Gavrilina ◽  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey N. Sokolov ◽  
Larisa A. Kuzmina ◽  
...  

Abstract Introduction. For more than a decade it's postulated that the addition oftyrosine kinase inhibitors (TKI) to chemotherapy has dramatically improved the long term outcome in Ph-positive adult acute lymphoblastic leukemia (Ph+ ALL). Nevertheless whether do we need chemotherapy at all and if yes - how intensive it should be, is still the matter of debates. The only randomized trial addressing this issue (GRAAL, Blood 2015, 125: 3711-3719) has demonstrated the lack of benefit of more intensive induction at all checkpoints: complete remission (CR) rate, major molecular complete remission (MMolCR), molecular complete remission (MolCR), progression disease (PD) and resistance. We have conducted two consecutive trials in Ph+ ALL aiming to evaluate the efficacy of more and less intensive chemotherapy approach in combination with constant non-stop 600 mg Imatinib application. Aim. Toanalyze of the protocol RALL-2009 with ITK and RALL-Ph+-2012 effectiveness in patients with Ph+ ALL. The primary objective was the major molecular complete remission (MMolCR) rate after induction (70th day), patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. Patients and methods. Since Jan 2010 till July 2016, 120 new cases of ALL were verified in our National Research Center for Hematology with 68 (56,7%) of them being B-cell precursors ALL and 25 diagnosed as Ph-positive (36,8%). Since 2010 till 2012, 10 Ph+ ALL pts (median age 35 years (19-68), m/f (50%)/(50%), CNS disease=1, WBC> 30*109/l=5(50%), bcr/abl transcript p190/p210/p190+210 6(60%)/3(30%)/1(10%)) were treated according to RALL-2009 protocol (ClinicalTrials.gov public site; NCT01193933) with parallel Imatinib. This protocol includes 8 cytostatic drugs and no intervals between treatment phases. Since 2012 till now 15 other pts (median age 40 years (17-61); m/f 7(46,7%)/8(53,3%); CNS disease=1, WBC>30*109/l=5(33,3%), bcr/abl transcript p190/p210/p190+210 9(60%)/5(33%)/1(7%)) were included in RALL- Ph+-2012 protocol, based mainly on 600 mg Imatinib with prednisolone, VNCR, L-asp, followed by 6-MP and MTX. Both protocols suggested the shift to Dasatinib (100-140 mg) after non-achievement of MolCR at day 70 of treatment. MolCR was stated if no bcr/abl chimeric transcript was detected by PCR with 10-4 sensitivity. All patients were considered as candidates for allogeneic HSCT if HLA-identical donor was available. Results. At day 70th disregarding the chemotherapy intensity there was 40% of MolCR on both protocols (RALL-2009 - n=4 and RALL-2012 - n=6). No death within 2 months of induction/consolidation were registered on less intensive protocol in comparison with 2 cases on RALL-2009. Hematological CR was achieved in all pts (except two early deaths on RALL-2009) - 23 of 25 (92%). There was one autologous HSCT in older pts, included in RALL-2012 (n=3, aGVHD and severe infections, at a median +4 months after HSCT and more than 12 months of CR duration). The 3y OS, DFS and relapse probability (RP) for all 25 pts constituted 37,8%, 32,5% and 52,1% (Fig. 1). The long-term outcome on both protocols (RALL-2009 and RALL-2012) was similar: OS - 45% vs 27,7% (p=0,27), DFS - 45% vs 22,1% (p=0,94), RP - 35,7% vs 57% (p=0,29), respectively (Fig.2). Conclusion. De-intensification of the chemotherapy does not affect the effectiveness of the therapy Ph-positive acute lymphocytic leukemia in era of the tyrosine kinase inhibitors. We haven't seen differences in achievement of molecular remission when we deescalated chemotherapy (40% vs. 40%). However, when we reduced toxicity of the chemotherapy in ALL-2012 protocol, we were able to realize more extra allo-BMT and it could improve long-term results of the therapy Ph+ ALL. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4926-4926
Author(s):  
Zahit Bolaman

Backround: Most of patients with acute myeloid leukaemia (AML) are elderly and older age is an negative prognostic factor for AML. There is no consensus about treatment of elderly patients with AML. In this study, we evaluated intensive treatment with cytosine arabinoside and idarubicine versus azacitidine treatment. Primary objectives were evaluation of disease free (DFS) and overall survival (OS), the rate of complete remission and the remission duration. Methods: 45 patients with AML were evaluated retrospectively. We examined peripheral blood smear, bone marrow aspirate and trephine, immunophenotyping and cytogenetic analysis, biochemical evaluation of renal and liver function and coagulation profile in pre-treatment period. Intensive treatment consisted of cytosine arabinoside 200 mg/m2/day for 7 days and idarubicin 12 mg/m2/ for 3 days. Bone marrow examination was done between 14-28 days for intensive treatment and 2-6 cyclus for azacitidine treatment. Consolidation treatment (1-3) was done after intensive treatment if the patients were remission. All patients were ≤ECOG 2. Growth factors were not routinely administered before, during or after chemotherapy. Statistical analyses, differences in baseline characteristics between groups were analyzed using the Student's t-test for continuous variables and differences in OS between groups were then analyzed using the likelihood ratio or log-rank tests. Table 1. The main properties of patients with elderly AML Treatment arm Mean age Sex M/F Leucocyte mean Hb gr/dl FAB (n) MDS history(n) LDH Complete remission Total 73±9 26/19 34.029 ±6870 8.53±1,2 M0:15, M1:6, M2:15,M4:4,M5:2 Yes:21 No:24 276±151 15 Intensive 72±7 18/10 44.176±12390 6.91±2 M0:6, M1:4, M2:12, M4:3, M5:1 yes: 14 299±101 13 Azacitidine 74±8 8/9 31.289±4013 8,95±1.6 M0:9, M1:2, M2:3, M4:1, M5:1 yes:7 256±72 2 Results: Total patient number were 45 and they were ≥ 65 years (yrs). Male/female ratio was 29/16. Two patients rejected leukemia treatment. One patient were not evaluated for treatment response. Intensive arm consisted of 26 patients and azacitidine arm 16 patients. Disease free survival and overall survival for intensive arm and azacitidine arm were 12,1±9,4, 16,7±22,4, respectively. The most importance factors were leucocyte counts, hb level. Picture 1-2: Disease free survival and overall survival for intensive arm and azacitidine arm Conclusions: These results showed that intensive treatment is more effective than azacitidine in elderly AML patients with ECOC≤2. There is need for large studies which include higher number of patients with AML in order to evaluate efficiency of intensive treatment. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
1974 ◽  
Vol 43 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Philip S. Schein ◽  
Bruce A. Chabner ◽  
George P. Canellos ◽  
Robert C. Young ◽  
Costan Berard ◽  
...  

Abstract The evaluation of the results of CVP and MOPP chemotherapy in 80 patients with advanced stages of non-Hodgkin’s lymphoma indicates that 36 (45%) achieved a complete remission. Twenty-eight per cent of the entire group of patients remain free of disease for periods ranging from 4 mo to over 7 yr, with a projected median duration of complete remission of 3½ yr. Significant differences in prognosis relative to histologic categories were found. Well-differentiated and nodular histology were positive determinants for improved median survival, confirming the over-all clinical validity of the Rappaport classification system for the non-Hodgkin’s lymphomas. The median survival for patients in the most clinically aggressive subgroups with diffuse histology is inferior to those with nodular patterns or well-differentiated cells. In this study it was demonstrated that it was possible to achieve a significant number of complete remissions even in the most aggressive histologic subgroups using combination chemotherapy, and these responses can be correlated with an extended disease-free survival without further therapy.


Blood ◽  
1982 ◽  
Vol 60 (4) ◽  
pp. 856-863 ◽  
Author(s):  
GV Dahl ◽  
DK Kalwinsky ◽  
S Murphy ◽  
AT Look ◽  
S Amadori ◽  
...  

Abstract A four-drug regimen, based on cell kinetic principles, induced complete remissions in 68 of 95 children (72%) with acute nonlymphocytic leukemia (ANLL). Patients entered remission after 2–5 weekly cycles of vincristine-daunorubicin (day 1) followed by sequential cytosine arabinoside and 6-azauridine (days 4–7). With continuation therapy of monthly vincristine-doxorubicin-cyclophosphamide, weekly cytosine arabinoside, and daily 6-mercaptopurine, the median duration of complete remission was 10 mo and the median survival time 21 mo. Portal triaditis, evident in 11 of 23 patients with liver biopsies, was associated with long remissions. A larger spleen size (greater than 5 cm) and a higher myeloblast labeling index (greater than 10%) at diagnosis were clearly related to shorter durations of remission. Splenectomy within 1 mo of remission had no statistically significant effect on the frequency of relapse or length of remission. Patients without central nervous system (CNS) leukemia at diagnosis, all treated prophylactically with intrathecal methotrexate, had a low frequency of initial CNS relapse (3/56, 5%). The 2-yr disease-free survival rate is 29% (20 of 68 patients attaining complete remission). fifteen patients have completed 2.5 yr of therapy, and each remains in continuous complete remission, off treatment, for 1+ -36+ mo. This induction chemotherapy was as effective as more intensive regimens, with the advantage of less toxicity and shorter periods of hospitalization.


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