scholarly journals Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 38-47 ◽  
Author(s):  
D Hoelzer ◽  
E Thiel ◽  
H Loffler ◽  
H Bodenstein ◽  
L Plaumann ◽  
...  
Keyword(s):  
Complete Remission ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Response To Therapy ◽  
Delayed Response ◽  
Childhood All ◽  
Remission Duration ◽  
Response To Chemotherapy ◽  
Adverse Influence

Abstract One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c- ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.

scholarly journals Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 38-47 ◽  
Author(s):  
D Hoelzer ◽  
E Thiel ◽  
H Loffler ◽  
H Bodenstein ◽  
L Plaumann ◽  
...  
Keyword(s):  
Complete Remission ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Response To Therapy ◽  
Delayed Response ◽  
Childhood All ◽  
Remission Duration ◽  
Response To Chemotherapy ◽  
Adverse Influence

One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c- ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.

A Pediatric Treatment of Ph-Negative Acute Lymphoblastic Leukemia (ALL) Is Effective and Safe In Adolescents and Young Adults (AYAs) until 29 Years of Age

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2125-2125
Author(s):  
Thomas Cluzeau ◽  
Nathalie Dhedin ◽  
Françoise Huguet ◽  
Emmanuel Raffoux ◽  
Sebastien Maury ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Central Nervous System Involvement ◽  
Early Response ◽  
Continuous Variable ◽  
Response To Therapy ◽  
Younger Adults ◽  
Response To Chemotherapy

Abstract Abstract 2125 Background: Over the last three decades, progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has considerably improved the outcome of children, leading to 5-year OS of more than 80%. Numerous comparisons, including the French LALA/FRALLE (Boissel et al. JCO 2001), have reported a better outcome in teenagers treated with pediatric as compared to standard historical adult ALL protocols. Even if modern pediatric-inspired adult ALL protocols have recently reported impressive improvements, especially in younger patients (Huguet et al. JCO 2009), the issue of whether younger adults (YAs) should be treated according to pediatric or adult protocols remains an open one. The aim of this study was first to evaluate the feasibility and the results of a non-modified pediatric protocol (the French FRALLE 2000) in adolescents and younger adults (AYAs, aged 15–29 years) treated in adult departments. Methods: From February 2001 to June 2010, 72 AYAs with Ph-negative ALL were treated according to the pediatric FRALLE 2000-BT protocol in 12 adult hematology units in France and Belgium. After a prednisone prephase and a four-drug induction (prednisone, daunorubicin, vincristine and L-asparaginase), patients in CR received a consolidation, a 1st delayed intensification, an interphase, a 2nd delayed intensification, and a maintenance chemotherapy during two years. Results: The median age was 19 years (range, 15–29 years). The cohort was separated in 2 subgroups: 44 adolescents aged 15–19 years and 28 young adults (YAs) aged 20–29 years. There were no significant differences between the adolescent and the YA populations in term of sex ratio, white blood cell count (WBC), central nervous system involvement, and phenotype (BCP- vs T-ALL). As expected, few recurrent cytogenetical abnormalities were identified in this population and did not differed between both subgroups. In the adolescent group, we identified 2 patients with t(4;11), 1 patient with t(1;19), and 3 patients with hypodiploïdy and/or neartriploïdy, whereas this repartition was 2/2/1 in YAs. Rates of good early response to prednisone were in 68% in adolescents and 61% in YAs (p=.52), while rates of good early response to chemotherapy were 80% and 86%, respectively (p=.51). No patient died during induction. Complete remission (CR) rate did not differ between subgroups (98% vs 100%, p=.42). With a median follow up of 4.8 years, 5-year EFS was 57% (41% in adolescents vs 79% in YAs, p=.03) and 5-year OS was 67% (56% and 82% respectively, p=.09). In patients with BCP-ALL, 5-year EFS was 60% (43% in adolescents vs 91% in YAs, p=.02) and 55% in T-ALL (57% vs 50% respectively, p=.81). Twelve patients (17%) received an allogeneic stem cell transplantation (SCT) in first CR (5 adolescents and 7 YAs). Four patients died in first CR, all after SCT, (2 adolescents and 2 YAs). In univariate analysis, a high WBC (continuous variable, p=.02) and a poor early response to chemotherapy (33% vs 63%, p=.02), but not phenotype or poor early response to prednisone, were significantly associated with a shorter EFS. In multivariate analysis, age (adolescents vs YA, p=.04), WBC (continuous variable, p=.0005), and poor early response to chemotherapy (p=.006) had still an impact on EFS. The poor outcome of adolescents compared to YAs, also observed in the French adult GRAALL protocol (not published), was not explained by differences in ALL characteristics, early response to therapy, or treatment-related toxicity. Conclusion: The pediatric protocol FRALLE 2000 is effective and safe for the treatment of selected AYAs with Ph-negative ALL referred to adult departments. The results observed in the YA population are promising, warranting prospective comparisons with the more recent pediatric-inspired adult protocols. The unexpected poorer outcome of adolescents deserves further investigations to explore a potential impact of the quality of care delivered in an adult environment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Simultaneous changes in expression levels of BAALC and miR-326: a novel prognostic biomarker for childhood ALL

2020 ◽  
Vol 50 (6) ◽  
pp. 671-678 ◽  
Author(s):  
Elaheh Sadat Ghodousi ◽  
Narges Aberuyi ◽  
Soheila Rahgozar
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Line ◽  
In Silico ◽  
Prognostic Biomarker ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Leukemia Cell Line ◽  
Childhood All ◽  
Expression Levels ◽  
Response To Chemotherapy

Abstract Objective Multidrug resistance and consequent relapse are two major obstacles for treating children with acute lymphoblastic leukemia, the most frequent childhood malignancy. MicroRNAs have potential regulatory roles in response to chemotherapy. The goal of this study was to determine the microRNA that may have effects on the expression level of brain and acute lymphoblastic leukemia (BAALC) and to investigate the in vitro and ex vivo association between their expression levels. Methods In silico tools were utilized to determine a putative miRNA targeting BALLC. Quantitative real-time polymerase chain reaction was used to investigate expression levels of BAALC and its predicted microRNA, miR-326, in bone marrow samples of 30 children with acute lymphoblastic leukemia and 13 controls, in addition to the resistant and parental CCRF-CEM cell lines. To assess the status of response to therapy, minimal residual disease was measured using single-strand conformation polymorphism. Results MiR-326 was selected due to the strong possibility of its interaction with BAALC according to the obtained in silico results. Statistical analysis showed a significant downregulation of miR-326 and overexpression of BALLC in drug-resistant acute lymphoblastic leukemia cell line and patients compared with the parental cell line and drug-sensitive patients, respectively (P = 0.015, 0.005, 0.0484 and 0.0005, respectively). The expression profiles of miR-326 and BAALC were inversely correlated (P = 0.028). Conclusions The results introduced the inversely combined expression levels of miR-326 and BAALC as a novel, independent prognostic biomarker for pediatric acute lymphoblastic leukemia (P = 0.007). Moreover, bioinformatics data showed a possible regulatory role for miR-326 on BAALC mRNA, which may possibly contribute to the development of drug resistance in patients with childhood acute lymphoblastic leukemia.

Pharmacokinetics and Pharmacodynamics of Oral Etoposide in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (7) ◽  
pp. 1340-1346 ◽  
Author(s):  
Mathew J. Edick ◽  
Amar Gajjar ◽  
Hazem H. Mahmoud ◽  
Matthijs E.C. van de Poll ◽  
Patricia L. Harrison ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Response To Therapy ◽  
Remission Induction ◽  
Pharmacokinetic Data ◽  
Oral Etoposide ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Childhood All

Purpose: To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL). Patients and Methods: Fifty-eight patients were randomly assigned to etoposide at 50 mg/m2/d with once- versus twice-daily doses for 22 days. On day 8, vincristine, asparaginase, and dexamethasone were started. Etoposide pharmacokinetics and pharmacodynamics were studied for 47, 28, and 26 patients on day 1, 8, and 22, respectively, of remission reinduction therapy. Results: Of 48 patients with pharmacokinetic data, 42 (87.5%) achieved complete remission, three (6.3%) failed to achieve remission, and three (6.3%) died during induction. Median etoposide day 8 area under concentration-time curve (AUC) and cumulative AUC tended to be greater (P = .06 and P = .07, respectively) in patients (n = 23) who achieved complete remission (24 and 522 μmol/L • h, respectively) than in patients (n = 3) who did not (14 and 303 μmol/L • h, respectively). Three of eight patients with plasma concentrations exceeding 1.7 μM (1 μg/mL) for more than 8 hours daily, compared with one of 20 patients with concentrations exceeding 1.7 μM for ≤ 8 hours daily, were unable to receive all 22 days of etoposide because of toxicity. There was no difference in the AUC at day 1 or day 8 with once- versus twice-daily doses (P = .55 and P = .86, respectively). Conclusion: A pharmacodynamic relationship exists between systemic etoposide exposure and response to therapy when oral etoposide is used as part of remission induction regimens for relapsed or refractory childhood ALL.

scholarly journals Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction [see comments]

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2348-2353 ◽  
Author(s):  
S Kojima ◽  
T Matsuyama ◽  
T Sato ◽  
K Horibe ◽  
S Konishi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Electron Microscopic ◽  
Normal Children ◽  
Response To Chemotherapy

Abstract The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet- specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.

scholarly journals High incidence of potential p53 inactivation in poor outcome childhood acute lymphoblastic leukemia at diagnosis

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 1155-1161 ◽  
Author(s):  
DI Marks ◽  
BW Kurz ◽  
MP Link ◽  
E Ng ◽  
JJ Shuster ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Leukemic Cells ◽  
Childhood All ◽  
P53 Gene Mutations ◽  
P53 Inactivation

Previous studies have indicated that p53 gene mutations were an uncommon event in acute lymphoblastic leukemia (ALL) in children. In one series of 330 patients, p53 mutations were seen in fewer than 3%. We analyzed bone marrow mononuclear cells derived from 10 children with ALL at diagnosis who subsequently failed to achieve a complete remission or who developed relapse within 6 months of attaining complete remission for p53 gene mutations and mdm-2 overexpression. We found that three children had p53 gene mutations, and four overexpressed mdm-2. Also, experiments comparing relative levels of mdm- 2 RNA and protein in these patients demonstrated that mdm-2 overexpression can occur at the transcriptional and posttranscriptional level in primary leukemic cells. Although we were unable to link Waf-1 RNA expression with p53 status in childhood ALL, our data show potential p53 inactivation by multiple mechanisms in a large percentage of these patients and demonstrate that these alterations can be detected at diagnosis. Inactivation of the p53 pathway may, therefore, be important in children with ALL who fail to respond to treatment and may be useful for the early identification of children requiring alternative therapies.

scholarly journals Chemotherapy of the blastic phase of chronic granulocytic leukemia: hypodiploidy and response to therapy

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1003-1009 ◽  
Author(s):  
GP Canellos ◽  
VT DeVita ◽  
J Whang-Peng ◽  
BA Chabner ◽  
PS Schein ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cytosine Arabinoside ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Blast Cell ◽  
Response To Therapy ◽  
Chronic Granulocytic Leukemia ◽  
Blastic Phase ◽  
Response To Chemotherapy ◽  
Granulocytic Leukemia

Abstract Thirty-two patients in the blastic phase of Philadelphia chromosome- positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine-- prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine-- prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.

Improved survival with cyclic chemotherapy for nonseminomatous germ cell tumors of the testis.

1985 ◽  
Vol 3 (3) ◽  
pp. 326-335 ◽  
Author(s):  
C J Logothetis ◽  
M L Samuels ◽  
D Selig ◽  
D Swanson ◽  
D E Johnson ◽  
...  
Keyword(s):  
Complete Remission ◽  
Germ Cell ◽  
Remission Rate ◽  
Germ Cell Tumors ◽  
Response To Therapy ◽  
Stage Iii ◽  
Disease Stage ◽  
Clinical Staging ◽  
Advanced Disease Stage ◽  
Nonseminomatous Germ Cell Tumors

Forty-eight patients with advanced nonseminomatous germ cell tumors of the testis received a combination of cyclophosphamide, doxorubicin, and cisplatin (CISCAII) and a modified combination of vinblastine and bleomycin (VBIV) cyclic chemotherapy. Forty-four (92%) have achieved a complete remission. No patient in complete remission has relapsed with a mean follow-up of 139.0 weeks (SEM 7.0 weeks). The patients were stratified according to the modified Samuels clinical staging criteria. Thirty-seven (77%) had advanced disease (stage III-B3 to III-B5), ten of whom had advanced visceral non-lung disease (stage III-B5). Chemotherapy was individualized by tumor volume and response to therapy. Two courses were delivered after complete remission or the development of a stable mass with negative serum biomarkers. Twenty-four patients (50%) were explored for a persistent and stable mass. No viable cancer was found; 15 (62%) had mature teratomas and nine (38%) had scar. No patients suffered from doxorubicin cardiotoxicity, clinical pulmonary bleomycin toxicity, or persistent cisplatin renal failure. Four patients died. One patient, an unrecognized drug abuser, died of toxicity. Three with far-advanced tumors died of progressive disease. CISCAII/VBIV cyclic chemotherapy is superior to chemotherapy with vinblastine, bleomycin, and cisplatin, resulting in a 92% complete remission rate and a significant reduction in long-term toxicity.

scholarly journals In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3861-3868 ◽  
Author(s):  
E Klumper ◽  
R Pieters ◽  
AJ Veerman ◽  
DR Huismans ◽  
AH Loonen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Poor Prognosis ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Childhood All ◽  
Acquired Drug Resistance ◽  
The Poor ◽  
Response To Chemotherapy

Cellular drug resistance is thought to be an important cause of the poor prognosis for children with relapsed or refractory acute lymphoblastic leukemia (ALL), but it is unknown when, to which drugs, and to what extent resistance is present. We determined in vitro resistance to 13 drugs with the MTT assay. Compared with 141 children with initial ALL, cells from 137 children with relapsed ALL were significantly more resistant to glucocorticoids, L-asparaginase, anthracyclines, and thiopurines, but not to vinca-alkaloids, cytarabine, ifosfamide, and epipodophyllotoxins. Relapsed ALL cells expressed the highest level of resistance to glucocorticoids, with a median level 357- and >24-fold more resistant to prednisolone and dexamethasone, respectively, than initial ALL cells, whereas the resistance ratios for the other drugs differed from 0.8- to 1.9-fold, intraindividual comparisons between initial and relapsed samples from 16 children with ALL showed that both de novo and acquired drug resistance were involved. Specific in vitro drug-resistance profiles were associated with high-risk relapsed ALL groups. In vitro drug resistance was also related to the clinical response to chemotherapy in relapsed/refractory childhood ALL. We conclude that drug resistance may explain the poor prognosis for children with relapsed/refractory ALL. These day may be helpful to design alternative treatment regimens for relapsed childhood ALL.

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