Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG‐ALL‐2002 study

Abstract

Background To eliminate cranial irradiation (CrRT)–related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)–directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL). Methods This study compared the treatment outcomes of patients overall and patients with a non–CNS‐1 status (CNS‐2, CNS‐3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG‐ALL‐2002 protocol by the introduction of the modification (era 1 [2002‐2008] with CrRT and era 2 [2009‐2012] with delayed first TIT and no CrRT). Results There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5‐year event‐free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non–CNS‐1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5‐year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2. Conclusions The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non–CNS‐1 status.

To delay or not to delay, that is the question for patients with acute lymphoblastic leukemia who do not receive prophylactic cranial irradiation

“…A comparison of contemporary trials of limited use and complete omission of prophylactic cranial irradiation shows similar rates of event‐free survival and CNS control (Table ). The likelihood of 5‐year event‐free survival and the cumulative risk of an isolated CNS relapse ranged from 72% to 89% and from 1% to 4.1%, respectively, in the 4 studies that omitted irradiation, whereas they ranged from 85% to 87.3% and from 1.4% to 2%, respectively, in the 3 trials in which up to approximately 10% of the patients were irradiated and from 82.5% to 85% and from 0.9% to 1.3%, respectively, when more than 10% were irradiated . Indeed, a 2016 meta‐analysis of more than 16,000 patients enrolled in clinical trials of 10 cooperative childhood ALL study groups indicated that prophylactic cranial irradiation had no impact on the overall survival or the cumulative risk of death, any adverse event, isolated CNS relapse, or combined CNS relapse in any subgroup of high‐risk patients with the exception of those with overt CNS leukemia (CNS‐3 status, 5 or more leukocytes per microliter with blasts) .…”

“…Encouraged by these early findings, most study groups now restrict prophylactic cranial irradiation to patients at high‐risk for CNS relapse, and some, such as the Taiwan Pediatric Oncology Group (TPOG), as reported in this issue of Cancer , have eliminated this treatment modality altogether . A comparison of contemporary trials of limited use and complete omission of prophylactic cranial irradiation shows similar rates of event‐free survival and CNS control (Table ).…”

“…Encouraged by these early findings, most study groups now restrict prophylactic cranial irradiation to patients at high-risk of CNS relapse, and some, such as the Taiwan Pediatric Oncology Group (TPOG), as reported in this issue of the Journal, 5 have eliminated this treatment modality altogether. 5–12 Comparison of contemporary trials of limited use versus complete omission of prophylactic cranial irradiation shows similar rates of event-free survival and CNS control (Table 1). The likelihood of 5-year event-free survival and the cumulative risk of an isolated CNS relapse ranged from 72% to 89% and 1% to 4.1%, respectively, in the 4 studies that omitted irradiation, 5,10,13,14 compared with 85% to 87.3% and 1.4% to 2% in the 3 trials in which up to approximately 10% of the patients were irradiated, 7,8,12 and with 82.5% to 85% and 0.9% to 1.3% when more than 10% were irradiated.…”

Human coronavirus OC43 infection associated pneumonia in a girl with acute lymphoblastic leukemia

“…The girl received chemotherapy according to the Taiwan Pediatric Oncology Group (TPOG) 2013-ALL-SR protocol, and spinal tap and triple intrathecal therapy was performed 7 to 10 days after chemotherapy. [ 3 ] No leukemic cells were found in the cerebral spinal fluid and the patient commenced prophylactic antibiotic and antifungal therapies with levofloxacin and micafungin on January 14th, when her leukocyte count was less than 1 × 10 9 cells/μl. She later developed febrile neutropenia on January 20th, and was administered teicoplanin and meropenem post collection of her blood for culture.…”

Treatment outcomes in children with Acute lymphoblastic leukemia with versus without coexisting Down's syndrome

“…For the management of pediatric ALL, different treatment protocols have been developed since years. [ 10 , 11 ] Treatment regimens comprised of multiple cytotoxic drugs including doxorubicin, cytarabine, methotrexate, vincristine, and etoposide. However, ALL children with co-existing DS may be more vulnerable to toxic side effects.…”