Long-Term Outcome in Children With Relapsed ALL by Risk-Stratified Salvage Therapy: Results of Trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group 87

2005 ◽  
Vol 23 (31) ◽  
pp. 7942-7950 ◽  
Author(s):  
Hagen Graf Einsiedel ◽  
Arend von Stackelberg ◽  
Reinhard Hartmann ◽  
Rüdiger Fengler ◽  
Martin Schrappe ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Early Time ◽  
Multicenter Trial ◽  
Cranial Irradiation ◽  
Intrathecal Chemotherapy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Leukemia Relapse ◽  
Time Point

Purpose Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria. Patients and Methods Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed. Results The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 ± 0.03 and 0.37 ± 0.03, respectively, with significant differences between the strategic groups (A, 0.18 ± 0.05 and 0.20 ± 0.05; B, 0.44 ± 0.05 and 0.52 ± 0.05; C, 0.35 ± 0.09 and 0.42 ± 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses. Conclusion With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.

The Long-Lerm Follow-Up of Childhood Acute Lymphoblastic Leukemia Treated in China with Chemotherapy under Poor Coverage of Medical Insurance: A Single Center Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4580-4580
Author(s):  
Yongmin Tang ◽  
Hua Song ◽  
Shuwen Shi ◽  
Shilong Yang ◽  
Jian Wei ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Medical Insurance ◽  
Cranial Irradiation ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
High Dose ◽  
Term Outcome ◽  
Childhood All ◽  
Long Term Outcome ◽  
Western Countries

Abstract Objectives to report the long-term outcome of childhood acute lymphoblastic leukemia (ALL) treated in our department between 1994 and 2004 under the poor coverage of medical insurance. Subjects and Methods A total of 151 pediatric patients aged 1.1 – 16.2 yrs with a median of 6 yrs were enrolled into this study. Gender: 93 males and 58 females with M:F ratio of 1.6:1. Patients were diagnosed based the morphology, immunophenotyping, cytogenetics and molecular biology markers and divided into standard risk (SR) group (104 cases) and high risk (HR) group (47 cases). Chemotherapy protocols consisted of VDLD (VCR 1.5mg/M2 qw on day 1, 8, 15, 22 + DNR 35mg/M2 qd on day 1, 2 (SR) or on day 1, 2, 3 (HR) + L-Asparaginase (6000U/M2 qod for 10 doses started on day 8 + Dexamethason 6mg/M2 orally for 28 days started on day1 with one week of tapering) for 4 weeks of induction followed by one week of CAT (CTX 800mg/M2 on day1 + Ara-C 50mg/M2 q12h on day1 ~ day7 for SR group or 1g/M2 q12h on day1 ~ day3 for HR group + 6-mercaptopurine 75mg/M2 qn on day1~day7) for consolidation. Then 3 courses of high-dose Methotrexate (HD-MTX) 3g/M2 for SR group or 5g/M2 for HR group for extramedullary leukemia prophylaxis were conducted followed by 3 successive courses of VM-26 150mg/M2 + Ara-C 300mg/M2 every two days for early intensification. In addition to HD-MTX, MTX+Ara-C+Dex in triplicate by intratheacal injection was also performed once a week during induction, consolidation and early/late intensification. Then, 2 weeks of VDLD for late intensification with 2–3 courses of HD-MTX and VM26 + Ara-C intensification with 2–3 courses of HD-MTX were alternated every 6 months until a total of 3 yrs for girls or 3.5 yrs for boys were reached. A total of 7~9 and 9~11 courses of HD-MTX were administered for patients with SR and HR groups, respectively for the extramedullary leukemia prevention. No cranial irradiation was used for the prevention of CNS leukemia. The maximum dosage of DNR was limited to 360 mg/M2. Results. All but two patients got complete remission (149/151, 98.68%) after 4 weeks of induction. The overall 5 yrs of event free survival (EFS) for both SR and HR groups was 70.60% with 85.65% for SR group and 61.36% for HR group. The overall relapse rate was 7/151 (4.63%) cases, of which CNS leukemia 2/151(1.32%) were identified. 3 patients went into second remission with a short duration and relapsed again and died shortly. No testicular leukemia relapse was identified. One patient (1/151, 0.66%) was found to have a secondary leukemia. Of all this patients, 58 patients (38.4%) had one year of medical insurance for a total of 80,000 yuan in RMB (about US$10,000) while 93 patients (61.6%) were all on their own finance. An average of 200,000 yuan in RMB (about US$20,000) was spent for each patient during the whole process of treatment. Conclusions Childhood ALL is curable disease even in patients with poor medical insurance and less intensive as compared to Western countries. The results are comparable to those reported in Western countries.

Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00

2010 ◽  
Vol 28 (22) ◽  
pp. 3644-3652 ◽  
Author(s):  
Renato Bassan ◽  
Giuseppe Rossi ◽  
Enrico M. Pogliani ◽  
Eros Di Bona ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Adult Patients ◽  
Negative Group ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Positive Group ◽  
Disease Free

Purpose Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. Patients and Methods Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. Results CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. Conclusion This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.

Time-Sequenced G-CSF (Lenograstim) for the Treatment of Adult Acute Lymphoblastic Leukemia - Seven Year Follow-Up of the Polish Adult Leukemia Group 4–96 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2733-2733
Author(s):  
Sebastian Giebel ◽  
Jerzy Holowiecki ◽  
Malgorzata Krawczyk-Kulis ◽  
Slawomira Kyrcz-Krzemien ◽  
Andrzej Hellmann ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Chemotherapy Protocol ◽  
Adult Leukemia ◽  
Leukemia Group

Abstract The goal of the study was to evaluate long-term outcome of patients treated within 4–96 trial by the Polish Adult Leukemia Group (PALG). Sixty four patients with newly diagnosed acute lymphoblastic leukemia (ALL) (median age 26 years, range 16–58) were randomly assigned to receive chemotherapy alone (n=31) or chemotherapy and glucosylated G-CSF (lenograstim) (n=33). Both groups were well-balanced in terms of age, initial WBC, immunophenotype and bcr/abl positivity. Induction therapy consisted of epirubicin+vincristin (Epi/Vcr) on days 1, 8, 15, 22, prednisone on days 1–28, L-asparaginase 8 doses starting from day 13; consolidation treatment included twice methotrexate+etoposide (Mtx/Vep), twice high dose cytarabine and cyclophosphamide (HDAraC/Ctx), CNS irradiation and intrathecal Mtx. In T-derived ALL, additional HDAraC/Ctx was administered instead of the first Mtx/HDAraC. During induction patients received G-CSF 150 μg/m2 sc. on days 2–6, 9–13, 16–20, 23-until the neutrophil recovery >1.0x109/L, starting 36 hours after Epi/Vcr, finishing 48 hours before the next dose; in consolidation - following each HDAraC/Ctx course on days 5–16. High risk patients having a donor were performed allogeneic hematopoietic cell transplantation in first complete remission, whereas those without a donor were given autologous transplant. At seven years the overall survival rate equalled 42% for G-CSF group and 24% for the controls (p=0.11). There was also a trend to higher probability of leukemia-free survival in advantage of patients receiving the cytokine (38% vs. 20%, p=0.17). The above differences might have resulted from: 1) Higher CR rate in the G-CSF group compared to the controls (94% vs. 87%), 2) Better adherence to the chemotherapy protocol (faster completion of induction-consolidation programme by 19 days, p=0.005, less dose reductions or delays), which in turn might have influenced the risk of relapse. We conclude that time sequenced G-CSF administration may improve long-term outcome of adult ALL patients although the study including larger population is required to confirm this hypothesis.

Incidence of Post-Thrombotic Syndrome Following Asymptomatic Thrombosis in Survivors of Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1631-1631
Author(s):  
Stefan Kuhle ◽  
Maria Spavour ◽  
Jacqueline Halton ◽  
Patricia Massicotte ◽  
Irene Cherrick ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Group I ◽  
Arm Circumference ◽  
History Of ◽  
Group Ii

Abstract BACKGROUND: Asymptomatic deep venous thrombosis (DVT) are well-known complications of treatment of acute lymphoblastic leukemia (ALL) in children. However, the clinical significance of radiographically detected, asymptomatic DVT is unclear and controversial, as there are no studies on long-term outcome of asymptomatic DVT in children available. There are two likely reasons for the studies not being done in this area. First, there is a lack of defined cohorts of pediatric patients screened for DVT and secondly, there is a great deal of difficulty in following patients over many years. The study, Prophylaxis with Antithrombin Replacement in Kids with ALL treated with L-Asparaginase (PARKAA) was a multicentre randomized controlled trial in which children with ALL were screened for DVT. As survivors of childhood cancer, the PARKAA cohort continues to be followed in their respective centers. Therefore, establishment of the PARKAA cohort (1997–99) and the ability to locate these patients provided a unique opportunity to study the long-term outcome of asymptomatic DVT. OBJECTIVE: To assess the incidence of PTS in children with ALL who previously had an asymptomatic DVT. The objective were approached in two ways. Firstly, to assess the outcome of asymptomatic DVT by determining the prevalence of PTS in children with a history of ALL with radiographically diagnosed DVT (PARKAA cohort); secondly, to corroborate the findings by determining the prevalence of PTS in an unselected group of survivors of childhood ALL. METHODS: Cross-sectional study in two separate populations: Group I comprised of children enrolled in the PARKAA multicentre study who had been screened for, and diagnosed with, DVT in the upper venous system. Group II consisted of non-selected patients < 21 years with a history of ALL followed at Stollery Children’s Hospital, Edmonton. Patients were invited for a follow-up at their treatment centre (Group I) or were assessed for PTS childhood cancer survivor clinic (Group II). PTS was assessed by two of the investigators (Group I) or by the attending oncologist (Group II), respectively, using a standardized scoring sheet. RESULTS: Group I: 13 PARKAA patients with a history of ALL and objectively diagnosed DVT were assessed for PTS (4 males; median age 11.9 years; median age at diagnosis of ALL 4.4 years). 7/13 patients had PTS (54%, 95%CI 25;81). All patients with PTS had collaterals on examination, 3 also had increased arm circumference. Group II: 41 patients with a history of ALL were enrolled (61% males; median age at diagnosis 3.0 years; 28% high-risk, 67% standard risk). Mean length of follow-up since diagnosis was 9.5 years. PTS was diagnosed in 10/41 (24%; 95%CI 11–38) patients. All patients with PTS had collaterals on examination, 5 (50%) also had increased arm circumference. CONCLUSIONS: There is a clinically significant prevalence of PTS in children with a history of ALL and radiographically diagnosed DVT. A significant proportion of survivors of ALL develop PTS, indicating previously undiagnosed DVT in this population.

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2690-2696 ◽  
Author(s):  
Ching-Hon Pui ◽  
John T. Sandlund ◽  
Deqing Pei ◽  
Dario Campana ◽  
Gaston K. Rivera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Dose ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Intrathecal Chemotherapy ◽  
Remission Induction ◽  
Cns Relapse ◽  
Risk Patients ◽  
Total Therapy

Abstract St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 × 109/L or more, or CNS-3 (5 or more leukocytes/μL with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lower-risk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% ± 2.6% (SE); the 8-year rate was 78.6% ± 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% ± 0.8%, and that of isolated plus combined CNS relapse was 3.0% ± 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% ± 1.3% in the lower-risk patients who received a cumulative dose of 1.2 g/m2 and 5.0% ± 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m2 (P = .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether. (Blood. 2004;104:2690-2696)

scholarly journals Long-term outcome of a pediatric-inspired regimen used for adults aged 18–50 years with newly diagnosed acute lymphoblastic leukemia

Leukemia ◽  
2014 ◽  
Vol 29 (3) ◽  
pp. 526-534 ◽  
Author(s):  
D J DeAngelo ◽  
K E Stevenson ◽  
S E Dahlberg ◽  
L B Silverman ◽  
S Couban ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome
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