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)

Triple Intrathecal Therapy Alone With Omission of Cranial Radiation in Children With Acute Lymphoblastic Leukemia

2014 ◽  
Vol 32 (17) ◽  
pp. 1825-1829 ◽  
Author(s):  
Hsi-Che Liu ◽  
Ting-Chi Yeh ◽  
Jen-Yin Hou ◽  
Kuan-Hao Chen ◽  
Ting-Huan Huang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Cumulative Risk ◽  
Cranial Irradiation ◽  
Intrathecal Therapy ◽  
Newly Diagnosed ◽  
Cns Relapse ◽  
Risk Patients ◽  
A Prospective Study

Purpose To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). Patients and Methods Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed. Results Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/μL with blasts in a nontraumatic sample) nor CNS-3 (≥ 5 WBCs/μL with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates ± SE were 84.2% ± 3.0% and 90.6% ± 2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4% ± 1.0%. Conclusion Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT.

Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.

1995 ◽  
Vol 13 (10) ◽  
pp. 2497-2502 ◽  
Author(s):  
V Conter ◽  
M Aricò ◽  
M G Valsecchi ◽  
C Rizzari ◽  
A M Testi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Intrathecal Chemotherapy ◽  
Intrathecal Methotrexate ◽  
Intermediate Risk ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Cns Disease ◽  
Cns Relapse

PURPOSE To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. PATIENTS Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) were patients with an RI > or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. RESULTS Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. CONCLUSION Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.

Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.

1993 ◽  
Vol 11 (5) ◽  
pp. 839-849 ◽  
Author(s):  
J Pullen ◽  
J Boyett ◽  
J Shuster ◽  
W Crist ◽  
V Land ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Chemotherapy ◽  
Oncology Group ◽  
Poor Risk ◽  
Cns Relapse ◽  
Risk Patients ◽  
Pediatric Oncology Group ◽  
Good Risk

PURPOSE The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Early Intensification of Intrathecal Chemotherapy Virtually Eliminates Central Nervous System Relapse in Children With Acute Lymphoblastic Leukemia

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 411-415 ◽  
Author(s):  
Ching-Hon Pui ◽  
Hazem H. Mahmoud ◽  
Gaston K. Rivera ◽  
Michael L. Hancock ◽  
John T. Sandlund ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Chemotherapy ◽  
Remission Induction ◽  
First Year ◽  
Cns Relapse ◽  
Continuation Treatment

Abstract Central nervous system (CNS) relapse has been an obstacle to uniformly successful treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We therefore intensified intrathecal chemotherapy (simultaneously administered methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to August 1994. The 64 patients (39%) who had 1 or more blast cells in cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without associated higher-risk features, received additional doses of intrathecal chemotherapy during remission induction and the first year of continuation treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid findings, also received additional doses of intrathecal chemotherapy during the first year of continuation treatment. Cranial irradiation was reserved for patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0.4% to 6.0%). The probability of surviving for 5 years without an adverse event of any type was 80.2% ± 9.2% (SE). Our results suggest that early intensification of intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level in children with ALL, securing a higher event-free survival rate overall.

Early Intensification of Intrathecal Chemotherapy Virtually Eliminates Central Nervous System Relapse in Children With Acute Lymphoblastic Leukemia

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 411-415 ◽  
Author(s):  
Ching-Hon Pui ◽  
Hazem H. Mahmoud ◽  
Gaston K. Rivera ◽  
Michael L. Hancock ◽  
John T. Sandlund ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Chemotherapy ◽  
Remission Induction ◽  
First Year ◽  
Cns Relapse ◽  
Continuation Treatment

Central nervous system (CNS) relapse has been an obstacle to uniformly successful treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We therefore intensified intrathecal chemotherapy (simultaneously administered methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to August 1994. The 64 patients (39%) who had 1 or more blast cells in cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without associated higher-risk features, received additional doses of intrathecal chemotherapy during remission induction and the first year of continuation treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid findings, also received additional doses of intrathecal chemotherapy during the first year of continuation treatment. Cranial irradiation was reserved for patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0.4% to 6.0%). The probability of surviving for 5 years without an adverse event of any type was 80.2% ± 9.2% (SE). Our results suggest that early intensification of intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level in children with ALL, securing a higher event-free survival rate overall.

scholarly journals Improved CNS Control of Childhood Acute Lymphoblastic Leukemia Without Cranial Irradiation: St Jude Total Therapy Study 16

2019 ◽  
Vol 37 (35) ◽  
pp. 3377-3391 ◽  
Author(s):  
Sima Jeha ◽  
Deqing Pei ◽  
John Choi ◽  
Cheng Cheng ◽  
John T. Sandlund ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cumulative Risk ◽  
Cranial Irradiation ◽  
Intrathecal Therapy ◽  
Cns Relapse ◽  
Increased Risk ◽  
Total Therapy ◽  
Higher Doses ◽  
Cns Control

PURPOSE Despite contemporary treatment, up to 10% of children with acute lymphoblastic leukemia still experience relapse. We evaluated whether a higher dosage of PEG-asparaginase and early intensification of triple intrathecal therapy would improve systemic and CNS control. PATIENTS AND METHODS Between 2007 and 2017, 598 consecutive patients age 0 to 18 years received risk-directed chemotherapy without prophylactic cranial irradiation in the St Jude Total Therapy Study 16. Patients were randomly assigned to receive PEG-asparaginase 3,500 U/m2 versus the conventional 2,500 U/m2. Patients presenting features that were associated with increased risk of CNS relapse received two extra doses of intrathecal therapy during the first 2 weeks of remission induction. RESULTS The 5-year event-free survival and overall survival rates for the 598 patients were 88.2% (95% CI, 84.9% to 91.5%) and 94.1% (95% CI, 91.7% to 96.5%), respectively. Cumulative risk of any—isolated or combined—CNS relapse was 1.5% (95% CI, 0.5% to 2.5%). Higher doses of PEG-asparaginase did not affect treatment outcome. T-cell phenotype was the only independent risk factor for any CNS relapse (hazard ratio, 5.15; 95% CI, 1.3 to 20.6; P = . 021). Among 359 patients with features that were associated with increased risk for CNS relapse, the 5-year rate of any CNS relapse was significantly lower than that among 248 patients with the same features treated in the previous Total Therapy Study 15 (1.8% [95% CI, 0.4% to 3.3%] v 5.7% [95% CI, 2.8% to 8.6%]; P = .008). There were no significant differences in the cumulative risk of seizure or infection during induction between patients who did or did not receive the two extra doses of intrathecal treatment. CONCLUSION Higher doses of PEG-asparaginase failed to improve outcome, but additional intrathecal therapy during early induction seemed to contribute to improved CNS control without excessive toxicity for high-risk patients.

Significance of Initial Lumbar Puncture on Day8 of Remission Induction Therapy in Childhood Acute Lymphoblastic Leukemia: The Results from the Tokyo Children’s Cancer Study Group L99-15 Protocol.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 914-914
Author(s):  
Daisuke Hasegawa ◽  
Atsushi Manabe ◽  
Akira Ohara ◽  
Katsuyoshi Koh ◽  
Chitose Ogawa ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lumbar Puncture ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Remission Induction ◽  
Study Group ◽  
Cancer Study ◽  
Cancer Study Group ◽  
Cns Relapse ◽  
The Impact

Abstract Traumatic lumbar puncture with the presence of leukemic blasts (TLP+) in the cerebrospinal fluid (CSF) has been shown to adversely affect the outcome of children with acute lymphoblastic leukemia (ALL). In the Tokyo Children’s Cancer Study Group (TCCSG), we adopted a strategy to defer the initial lumbar puncture (LP) and intrathecal (IT) chemotherapy until 1 week after prednisolone (PSL) monotherapy so that circulating blasts were substantially reduced when the initial LP/IT was performed. The result of L89-12 study was previously reported, in which the incidence of TLP+ was significantly diminished but the impact on the rate of central nervous system (CNS) relapse was not determined because over 80% of patients received cranial irradiation (CRT). We analyzed the result of L99-15 study in which CRT was employed in only 16% of patients. Seven hundred and fifty-five children with newly diagnosed ALL were enrolled onto the TCCSG L99-15 study between April 1999 and June 2003. Patients received the initial IT administration of methotrexate, hydrocortisone, and cytarabine on day 8 following PSL monotherapy. Patients with CNS2 (<5 leukocytes/microL of CSF with leukemic blasts) received additional IT therapy. Patients with CNS3 (>5 leukocytes/microL of CSF with leukemic blasts) or CNS1s (negative CSF finding, with cranial nerve palsy) received additional IT therapy and CRT. Patients with TLP+ did not require any reinforcement of CNS-directed therapy. The frequency of CNS1s, CNS2, CNS3, or TLP+ was 0.5%, 1.1%, 0.5% and 0.8%, respectively. These figures were almost equal to the results from L89-12 study and much lower than those reported by other study groups such as BFM. Of 22 patients (2.9% of all) classified as CNS positive group (CNS-1s, -2, -3 and TLP+), only one patient had a CNS relapse concurrently with bone marrow (BM) relapse, whereas 22 of 723 patients classified as CNS negative had CNS relapse (isolated 12, combined with BM 10). Overall, 4-year event-free survival rate was 78.2 +/− 1.6%, and 4-year cumulative incidence of overall CNS relapse was 3.3 +/− 0.7%. Our strategy may underestimate the frequency of CNS leukemia at diagnosis, however, unnecessary intensification of CNS treatment may be avoided while overall CNS relapse rate is quite low in spite of restricted indication for cranial irradiation.

Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1285-1294 ◽  
Author(s):  
Donald H. Mahoney ◽  
Jonathan J. Shuster ◽  
Ruprecht Nitschke ◽  
Stephen Lauer ◽  
C. Philip Steuber ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Effective Therapy ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
Continuation Therapy ◽  
Increased Risk ◽  
Significant Difference ◽  
Prevention Of Relapse

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m2 plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1,000 mg/m2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years. RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.

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.

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