Long Term Survival Using Intensive Multiagent Chemotherapy for Relapses of Pediatric Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1953-1953 ◽  
Author(s):  
Susan R. Rheingold ◽  
Nancy J. Bunin ◽  
Richard Aplenc ◽  
Ann M. Leahey ◽  
Beverly J. Lange
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Term Survival ◽  
Childhood All ◽  
Long Term Survival ◽  
Chemotherapy Protocol ◽  
Multiagent Chemotherapy ◽  
Standard Risk

Abstract Relapses of childhood ALL that occur on therapy are associated with a dismal survival. To improve the prognosis for these patients, we developed an intensive multiagent chemotherapy protocol consisting of an induction with idarubicin, vincristine (VCR), dexamethasone (DEX), and peg-asparaginase (PEG). Consolidation included high-dose cytarabine (ARA-C), etoposide (VP-16), and PEG followed by VCR and methotrexate (MTX). After an interim maintenance (IM), induction and consolidation were repeated followed by maintenance therapy lasting two years. Maintenance and IM consisted of alternating two week cycles of VP-16, ARA-C, and PEG, with MTX ,VCR, DEX, and PEG. Between 1992 and 2002, 53 pts (32M, 21F) received treatment according to this protocol, 21 of whom were treated as part of the original study (Leahey AM et al., Med Ped Onco34(5):313–8, 2000). Median time to relapse was 37 months from diagnosis (range 12–86 mos). Twenty-one pts were on therapy at relapse and 25 pts were <36 months from diagnosis. Relapses included isolated bone marrow (BM) (32 pts), BM and central nervous system (CNS) (9 pts), BM and testicular (3 pts), and extramedullary (EM) (9 pts). By present day criteria 26 pts were standard risk (SR), 23 were high risk (HR), and 4 were infants. Two patients died in induction, and 2 never achieved a second remission. All others achieved remission by the end of induction (92%). Five-year event-free survival (EFS) and overall survival (OS) are both 56% +/−7% (CI 41%–68%), at a mean of 47 months from relapse (range 0–141 mos). Patients with a first complete remission (CR1) duration <36 months have an EFS of 40% +/−10% (CI 21%–58%); >36 months CR1 is associated with an EFS of 70% +/−9% (CI 50%–84%). Of the events in all pts who initiated therapy,13 were from refractory/recurrent ALL (25%), and 10 pts died of toxicity (19%). Four pts died from chemotherapy induced toxicity (8%), and 6 died from transplant (BMT) related toxicities (11%). Fourteen pts in second remission proceeded to BMT at a mean of 5 months from relapse (range 4.5–8 mos), and 7 of these pts remain in CR2. Of the 39 pts who continued on chemotherapy, 6 pts (35%) with CR1<36 months remain in CR2 and 16 patients (57%) with CR1>36 months remain in CR2 or 3. The 19 pts who were treated on modern standard risk (SR) protocols (CCG-1881 to present) were more salvagable than their 20 high risk (HR) counterparts (CCG-1882 to present). Five year EFS for SR and HR pts is 67% +/−8% (CI 48%–80%) and 38% +/−12% (CI 16%–59%) respectively. Intensive rotating therapy with reinduction and reconsolidation improves EFS. Children with early EM relapses of ALL, CR1 > 36 months, and SR patients all have very good long term survival. Novel therapies need to be integrated into intensive relapse protocols for children with early BM relapse and children treated upfront on HR protocols. Figure Figure Figure Figure

Results of Treatment with Tyrosine Kinase Inhibitors(TKIs) in Combination with Intensive Chemotherapy in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia(Ph+ALL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1503-1503
Author(s):  
Taiichi Kyo ◽  
Takeshi Okatani ◽  
Kouhei Kyo ◽  
Ryouta Imanaka ◽  
Mitsuhiro Itagaki ◽  
...  
Keyword(s):  
Present Report ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Term Survival ◽  
Long Term Survival ◽  
Chemotherapy Group ◽  
First Choice ◽  
Induction Regimen

Abstract Abstract 1503 (Objective) The treatment outcome of patients with Ph+ ALL has significantly improved since the advent of TKIs such as imatinib and dasatinib. However, the long-term survival of these patients is not necessarily high when bone marrow transplantation (BMT) is not performed. The present study was aimed at developing an effective combination of a TKI and chemotherapy for long-term survival of patients with Ph+ ALL but ineligible for BMT. (Subjects and Methods) Forty-three consecutive patients (18 men, 25 women) with previously untreated Ph+ ALL who visited our hospital between June 2001 and February 2011 were treated. The age range was 13 to 84 years (median: 57), and 21 were 60 years or older. Measurement of BCR-ABL fusion transcript levels was performed immediately in these patients, and imatinib (IM) was started at 600 mg/body/day (given daily as a rule) as soon as the patient tested positive. A remission induction regimen (chemotherapy) used commonly in acute myeloblastic leukemia (AML) patients at our hospital was combined with TKIs in the first 14 patients. Another remission induction regimen often used in ALL patients at our hospital was then combined with TKIs in the subsequent 29 patients. The AML remission induction regimen used idarubicin (IDR) at 12 mg/m2 for 4 days, behenoyl-ara-C (BH-AC) at 350 mg/m2 for 10 days, and prednisolone (PSL) at 40 mg/body (P.O.) for 10 days. PSL was initially given at 100 mg/body (P.O.) and then gradually reduced in the ALL remission induction regimen. Vincristine (VCR) at 1.3 mg/m2 (Days 1, 8, 15, and 22), daunorubicin at 60 mg/m2 (Days 1, 2, and 3), cyclophosphamide at 1200 mg/m2 (Day 2), and L-asparaginase at 3000 μ/m2 (Days 11, 13, 16, 18, and 20) were administered. The remission induction therapies were given in a sterile room. Macrophage colony-stimulating factor was given for 7 days from Day 11 and granulocyte colony-simulating factor from Day 19. A post-remission therapy commonly administered to AML patients at our hospital was given after remission for 1 year (ASH, 2009, abstract, no. 1052). High-dose cytarabine (at 2 g/m2 BID for 5 days but at 1 g/m2 BID in patients aged 60 years or older) (HD-AC) and mitoxantrone (MIT) at 7 mg/m2 × 3 were initially administered after remission. Maintenance/consolidation therapy was given by alternating BH-AC at 350 mg/m2 × 4 + aclarubicin at 20 mg/body × 6 and BH-AC at 350 mg/m2 × 4 + IDR at 10 mg/m2 × 1 + VCR at 1.3 mg/m2 (each for 35 days). IM was given daily at 600 mg/day simultaneously with the post-remission therapy. Dasatinib was used in the post-remission therapy of 8 patients at 140 mg/day. All of the TKIs were given to patients for 3 years after completion of chemotherapy. (Results) Complete remission (CR) was achieved in 41/43 (95%). CR was achieved in 13 out of 14 (93%) patients treated with the AML regimen and 28 out of 29 (97%) treated with the ALL regimen. DIC occurred in 31/41 (76%) during remission induction therapy. The follow-ups of patients achieving CR lasted for 5 to 128 months (median: 24 months). Ten patients (aged 25 to 54 years [median: 37]) underwent BMT at first CR. Thirty-one patients (aged 13 to 84 years [median: 63]) were assigned to the chemotherapy group. The 10-year overall survival (OS) calculated by the Kaplan-Meier method was 57% for 41 patients who achieved CR, 66% for 20 patients younger than 60 years, and 49% for 21 patients aged 60 years or older. The OS was 80% for 10 patients who underwent BMT at first CR and 47% for 31 patients in the chemotherapy group. The 50% OS of the chemotherapy group was 36 months. The 10-year event-free survival (EFS) was 50% for patients who achieved CR, 80% for patients who underwent BMT at first CR, and 43% for the chemotherapy group. The 50% EFS of the chemotherapy group was 33 months. Fifteen patients have relapsed, and a new chromosomal aberration was observed at relapse in 11/13 (85%). (Discussion) The results of the present report indicate that BMT is the first choice for post-remission therapy of Ph+ ALL. Fifty percent of patients aged 60 years or older, who account for about half of the patients with Ph+ ALL, have achieved long-term survival with the prolonged TKI + chemotherapy used in the present report. Relapse was also rare among patients who received the combination and maintained CR for 3 years or longer. A combination of an appropriate TKI and a chemotherapy regimen as well as careful monitoring for complications is likely to further extend the survival of patients with Ph+ ALL. Disclosures: No relevant conflicts of interest to declare.

Intensified and Shortened Cyclical Chemotherapy for Adult Acute Lymphoblastic Leukemia

2002 ◽  
Vol 20 (10) ◽  
pp. 2464-2471 ◽  
Author(s):  
Charles Linker ◽  
Lloyd Damon ◽  
Curt Ries ◽  
Willis Navarro
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Previous Treatment ◽  
Intrathecal Methotrexate ◽  
High Dose ◽  
Chemotherapy Protocol ◽  
New Treatment ◽  
Standard Risk

PURPOSE: To assess the efficacy and toxicity of a new treatment program of intensified and shortened cyclical chemotherapy (protocol 8707) in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Previously untreated adults ≤ 60 years old with ALL were treated with a four-agent induction chemotherapy regimen. This was followed by cyclical postremission therapy with high-dose cytarabine/etoposide; high-dose methotrexate/6-mercaptopurine; and daunorubicin, vincristine, prednisone, and asparaginase. Maintenance chemotherapy with oral methotrexate and 6-mercaptopurine was continued for 30 months. CNS prophylaxis was given with intrathecal methotrexate in addition to the systemic chemotherapy indicated above. RESULTS: Seventy-eight of 84 patients (93%) achieved complete remission. With a median follow-up of 5.6 years, 5-year event-free survival (EFS) of all remission patients is 52%. Patients with high-risk features including adverse cytogenetics, failure to achieve remission with the first cycle of chemotherapy, and B-precursor disease with WBC counts more than 100,000/μL all relapsed unless taken off study for transplantation. For patients without these high-risk features, 5-year EFS was 60%. Compared with our previous treatment regimen, results appear to be improved for patients with standard-risk B-precursor disease (5-year EFS, 66% v 34%; P = .01). CONCLUSION: Intensified and shortened chemotherapy may improve the outcome for patients with ALL with B-precursor disease lacking high-risk features. Further trials of this regimen are warranted.

Long‐term survival of two patients with recurrent high‐risk neuroblastoma

2021 ◽  
Author(s):  
Tomonobu Sato ◽  
Kazuya Hara ◽  
Go Ohba ◽  
Hiroshi Yamamoto ◽  
Akihiro Iguchi
Keyword(s):  
High Risk ◽  
Term Survival ◽  
Long Term Survival

scholarly journals The Colony-Stimulating Factor 3 Receptor M696T Mutated in a Patient with Ph+ Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Xin Chen ◽  
Bichen Wang ◽  
Aiming Pang ◽  
Erlie Jiang ◽  
Yajing Chu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Colony Stimulating Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Transformation ◽  
Stimulating Factor

Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in a variety of myeloid disorders, such as severe congenital neutropenia (SCN), chronic neutrophilic leukemia (CNL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and atypical chronic myelogenous leukemia (aCML). Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. We report a case of philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with the M696T mutation in CSF3R gene and assess the pathogenicity of the CSF3R M696T mutation in Ph+ ALL. Experimental Design: Here we report on a 32-year-old female who presented with asthenia. The initial hematological workup revealed white blood cell (WBC) count of 97 x 109/L (normal range 4-10 x 109/L). There was 84% prolymphocyte in the bone marrow. The immunophenotype of the blasts as judged from flow cytometry was in accordance with a B-ALL. The fusion gene for BCR-ABL P210 was positive. Hot mutation closely related to diseases was: CSF3R (nucleotide change c.2087 T&gt;C, amino acid change p.M696T, mutation frequency 50.4%). Cytogenetic analysis showed 46, XX, t (9;22) (q34;q11). The patient was diagnosed as Ph+ ALL with the CSF3R M696T mutation and achieved Long-term survival after unrelated donor hematopoietic stem cell transplantation. Meanwhile we performed a series of experiments using murine interleukin 3 (IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation. The phosphorylation of STAT3 was analyzed by G-CSF dependence assays and immunoblot analysis to evaluate the CSF3R M696T mutation contribution to the tumor transformation ability of Ba/F3 cells. Results: This patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor (TKI) and long-term survival by unrelated donor transplantation. We confirmed the presence of a CSF3R M696T germline mutation in this patient, and the mutation was inherited from her mother. The experiments in vitro result showed the CSF3R M696T mutation harbors marginal contribution to the tumor transformation ability of Ba/F3 cells. CSF3R M696T mutation was neutral in tumor transformation ability. Conclusions: We believe that TKI is still effective in patients with the CSF3R M696T mutation in Ph+ ALL. Donor with CSF3R M696T mutation might still be selected. Disclosures No relevant conflicts of interest to declare.

Abstract 2143: Improved Long-Term Survival in a High Risk Population Following Drug Eluting Stent Availability

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Maheer Gandhavadi ◽  
Kendrick A Shunk ◽  
Edward J McNulty
Keyword(s):  
High Risk ◽  
Independent Predictor ◽  
Drug Eluting Stent ◽  
High Risk Population ◽  
Term Survival ◽  
Risk Population ◽  
Long Term Survival ◽  
Drug Eluting ◽  
The Impact

Background Data regarding the impact of drug eluting stent (DES) use on long-term outcomes outside trial populations are limited. Methods 1,547 consecutive patients underwent stent implantation from January 2000 until December 2006 at the San Francisco Veterans Affairs Medical Center. To assess the impact of DES availability on mortality, that population was partitioned into a pre-DES cohort (N=591) and a post-DES availability cohort (N=956). Kaplan-Meier survival curves for the two cohorts were compared. Results The entire population was relatively high risk: 37% had diabetes, 38% a reduced ejection fraction, and 53% a prior MI or elevated troponin prior to the procedure. Median follow up was 4.7 years for the pre-DES cohort and 1.8 years for the post-DES cohort. DES were used in 83% of procedures in the post-DES cohort. Survival improved significantly in the post-DES cohort (P = .04, Log Rank)(see Figure ). Baseline characteristics, procedural variables and discharge medications were analyzed in a Cox proportional hazards model (see Table ). DES use was an independent predictor of improved survival (Hazard Ratio for death 0.52, 95% CI .28–.95). Conclusions In an unselected, high risk population, long-term survival improved following the availability of drug eluting stents. After adjusting for potential confounding factors, DES use was an independent predictor of improved survival. Independent Predictors of Death in all 1,547 Patients

scholarly journals BST-236, a novel cytarabine prodrug for patients with acute leukemia unfit for standard induction: a phase 1/2a study

2019 ◽  
Vol 3 (22) ◽  
pp. 3740-3749 ◽  
Author(s):  
Tsila Zuckerman ◽  
Ron Ram ◽  
Luiza Akria ◽  
Maya Koren-Michowitz ◽  
Ron Hoffman ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Leukemia ◽  
Phase 1 ◽  
Intensive Therapy ◽  
High Dose ◽  
Term Survival ◽  
Long Term Survival ◽  
Key Points ◽  
High Dose Cytarabine

Key Points The majority of older adults or unfit acute leukemia patients are not offered intensive therapy, resulting in dismal long-term survival. A novel cytarabine prodrug BST-236 enables delivery of high-dose cytarabine and appears to be safe and efficacious in these patients.

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