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>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.

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.

Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas, a cohort study

2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  
Keyword(s):  
Dopamine Agonists ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Pituitary Surgery ◽  
Cerebrospinal Fluid Leakage ◽  
Neurosurgical Department ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free

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.

Second Primary Melanomas: Incidence and Outcome

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 ◽  
...  
Keyword(s):  
Early Stage ◽  
Primary Melanoma ◽  
Disease Free Survival ◽  
Second Primary ◽  
Free Survival ◽  
Kaplan Meier ◽  
Ongoing Surveillance ◽  
Post Hoc ◽  
Disease Free

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.

Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.

1992 ◽  
Vol 10 (1) ◽  
pp. 41-46 ◽  
Author(s):  
G J Schiller ◽  
S D Nimer ◽  
M C Territo ◽  
W G Ho ◽  
R E Champlin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
First Remission ◽  
Disease Free

PURPOSE Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.

scholarly journals Significance of “de novo” appearance of thyroglobulin antibodies in patients with differentiated thyroid cancer

2020 ◽  
Vol 35 (3) ◽  
pp. 41-49
Author(s):  
Lorenzo Scappaticcio ◽  
Pierpaolo Trimboli ◽  
Frederik A. Verburg ◽  
Luca Giovanella
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
De Novo ◽  
Disease Free Survival ◽  
Thyroglobulin Antibodies ◽  
Free Survival ◽  
Similar Disease ◽  
Structural Disease ◽  
Disease Free

Objective Clinical and laboratory guidelines recommend thyroglobulin antibodies (TgAbs) measurement with every thyroglobulin (Tg) measurement for the follow-up of differentiated thyroid cancer (DTC) patients. However, no evidence exists on the need for perpetual TgAbs testing in patients who are TgAb-negative at baseline. Our study was carried out to evaluate the prevalence, the dynamic changes, and the clinical significance of TgAbs that appeared de novo during the follow-up of DTC patients who were TgAb-negative at baseline. Methods The data of DTC patients with negative pre-ablation TgAbs were reviewed retrospectively. The main characteristics of patients with both transient and sustained de novo TgAbs appearance were analyzed. DTC patients with persistently negative TgAbs served as controls. Results Among 119 patients with pre-ablation negative TgAbs, 14 cases (11.7%) with de novo TgAbs appearance (10 and 4 patients with a transient and sustained de novo TgAbs appearance, respectively) were detected. No differences in disease-free survival were observed in patients with de novo TgAbs appearance compared to controls. The TgAbs peak value was higher in patients with sustained de novo appearance compared to patients with transient de novo. Two of 14 patients with de novo TgAbs developed structural disease with concurrently detectable Tg in both cases. Conclusions Transient de novo TgAbs appearance is not infrequent during DTC patients’ follow-up, and it has no apparent clinical impact. Sustained de novo TgAbs appearance is rare and may predict structural recurrences; however, similar disease-free survival was observed in patients with sustained de novo TgAbs and TgAb-negative DTC patients.

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.

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.

Outcomes in CCG-2961, a Children’s Cancer Group Phase III Trial for Untreated Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 169-169 ◽  
Author(s):  
Beverly J. Lange ◽  
Franklin O. Smith ◽  
Patricia A. Dinndorf ◽  
Carola A.S. Arndt ◽  
Dorothy R. Barnard ◽  
...  
Keyword(s):  
De Novo ◽  
Interleukin 2 ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Remission Induction ◽  
High Dose ◽  
Free Survival ◽  
Cancer Group ◽  
De Novo Aml

Abstract CCG-2961 tested an intensively timed induction therapy consisting of cytarabine (AC), etoposide, thioguanine, dexamethasone, idarubicin and daunorubicin. Patients in remission after induction were randomized to a second induction course (Arm A) or a 3-drug combination of fludarabine, AC, and idarubicin (Arm B). Course 3 for patients with related donors was bone marrow transplantation (BMT); for those without donors, high dose AC/l-asparaginase. After Course 3 patients without donors were randomized to 14 infusions of Interleukin 2 (IL2) over 18 days or follow-up. CNS prophylaxis was intrathecal AC. Eligibility included all subtypes of de novo AML except acute promyelocytic leukemia and AML in patients with Down syndrome. CCG-2961 opened in Oct.1996 and closed in Dec. 2002. The DSMC suspended the study between Oct. 1999 and May 2000 while the 2961 Committee developed supportive care policies to reduce treatment-related mortality (TRM). CCG-2961 enrolled 900 de novo patients aged 3 days to 21 years, with 495 and 405 patients accruing pre-and post suspension respectively. Remission induction rate is 88.5%. With median follow-up of 3.6 years (range: 0 – 8.1 years), event-free survival (EFS) at 3 years is 44±3% and survival (OS) 57±3%. Disease-free survival (DFS) following Course 2 Arms A and B are not different, although relapse is significantly higher in Arm A (7.3% .vs. 3.1% P=0.018) and TRM more common in Arm B (7.9% vs.4.2% P=0.059), despite 7 less days of neutropenia in Arm B (P&lt;0.001). DFS is 65±9% for patients with a donor versus 50±5% for patients without a donor (P=0.005); respective OS, 74±8% and 66±5% (P=0.221). However, among 98 patients in CR1 with t(8;21) or inv(16) cytogenetics, outcomes in those without and with a donor were no different: DFS (61±12% vs. 72±18%, P = 0.49) and OS (78±10% vs. 77±17%, l P= 0.85). DFS with and without IL2 is 55±9% and 60±8%(P=0.606). Outcomes improved progressively over time. EFS pre- and post-suspension are 41±4% and 47±5%(P=0.038); OS, 52±5% and 63±5%(P=0.005); TRM is 17±3% pre- and 12±3% post-suspension (P=0.039). Factors predictive of inferior EFS are age &gt;17 years, Afro-American and Hispanic ethnicity, body mass index &lt;10th or &gt;95th percentile for age, absence of related marrow donor, WBC &gt; 50,000/mm3, karyotype with −7/7q, −5/5q- or &gt; cytogenetic 5 abnormalities, FLT3/ITD, &gt;15 % morphologic blasts on day 14 or &gt;0.5% immunologically detectable blasts at the end of induction. CCG-2961 confirms the efficacy and high TRM of intensively timed therapy. Neither fludarabine nor IL2 increases DFS or OS, and availability of a donor does not improve outcomes in those with favorable cytogenetics.

Treatment of Therapy-Related Myeloid Neoplasms with High-Dose Cytarabine/Mitoxantrone Followed by Hematopoietic Cell Transplantation (HCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1030-1030
Author(s):  
Lucy A Godley ◽  
Uchenna O. Njiaju ◽  
Margaret Green ◽  
Howard Weiner ◽  
Shang Lin ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Myeloid Neoplasms ◽  
High Dose Cytarabine ◽  
Autologous Hct ◽  
Disease Free

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.

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