Radiation dose to the thyroid in the treatment of acute lymphoblastic leukemia (ALL)

Sixteen children who received cranial irradiation for CNS prophylaxis of leukemia were evaluated for dose of radiation received to the thyroid. Radiation dose received by the thyroid varied between 2.8 to 7.5% of the given dose to the cranium. This is sufficient radiation to increase the risk of long-term thyroid pathology.     

Cognitive Function in Long Survivors of Childhood Acute Lymphoblastic Leukemia

Thirty long survivors of childhood acute lymphoblastic leukemia were compared with their healthy siblings on cognitive and neuropsychological measures. The subjects were comparable in treatment variables except for type of central nervous system prophylaxis received. Thirteen were given radiotherapy with intrathecal medication, and seventeen received only intrathecal treatment. Patients receiving only intrathecal medication did not differ from controls. Patients receiving radiotherapy scored lower on several measures including Wechsler Full Scale and Performance IQ. Irradiated girls scored lower than boys on most measures. Children whose clinical management has included radiation therapy appear to be at risk for later mild cognitive deficits. No consistent pattern of neuropsychological deficits has emerged and observed deficit patterns may reflect individual vulnerabilities.     

Transplant‐related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25‐year retrospective review

Background

Over the last 25 years, donor source, conditioning, graft‐versus‐host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high‐risk patients in first and subsequent remission. There is a large burden of infectious and pre‐HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased.

Procedure

A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8‐year periods (Period 1: 1/1/1984–31/8/1992, Period 2: 1/9/1992–30/4/2001, Period 3: 1/5/2001–31/12/2009).

Results

Despite a significant increase in unrelated donor HSCT, event‐free and OS over 25 years improved significantly. (EFS 31.6–64.8%, P = 0.0027; OS 41.8–78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time.

Conclusion

EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post‐HSCT are unchanged, and remain the focus for improvement. Pediatr Blood Cancer 2013;160:1520–1527. © 2013 Wiley Periodicals, Inc.     

Treatment of young children with CNS‐positive acute lymphoblastic leukemia without cranial radiotherapy

Background

Due to the long‐term sequelae of cranial radiotherapy (CRT), contemporary treatment protocols for children with acute lymphoblastic leukemia (ALL) aim to limit the use of prophylactic CRT. For patients with central nervous system (CNS) involvement with ALL at diagnosis, the use of CRT remains common. Children <5 years of age are a particularly challenging subgroup in whom the consequences of CRT can be devastating.

Procedure

This study retrospectively describes the overall (OS) and event‐free survival (EFS) of young children (1–5 years) who were treated for CNS‐positive ALL at the Hospital for Sick Children between 2000 and 2013.

Results

Of a total of 19 patients, two were treated with upfront CRT, both as part of the conditioning regimen prior to HSCT. All patients received intensification of CNS‐directed chemotherapy by triple intra‐thecal chemotherapy (84.2%), use of dexamethasone in induction (57.9%) and maintenance (66.7%), and high‐dose methotrexate (77.8%). The OS was 84.2 ± 8.4% and EFS was 79.0 ± 9.4% with a median follow‐up time of 4.3 years (range, 2.6–8.2). The cumulative incidence of CNS relapse was 5.2 ± 5.1%.

Conclusions

We conclude that omission of CRT from the treatment of young children with ALL involving the CNS is associated with acceptable survival and avoids potentially devastating late effects in this group. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.     

Rapid Capture Next‐Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B‐Cell Precursor ALL

Comprehensive next‐generation sequencing (NGS) applications have recently identified various recurrent kinase and cytokine receptor rearrangements in Ph‐like B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL) amenable to tyrosin kinase inhibitor treatment. For rapid diagnostics of kinase pathway aberrations in minimal residual disease (MRD) high‐risk BCP‐ALL, we developed a PCR‐independent NGS custom enrichment capture panel targeting recurrent genomic alterations, which allows for the identification of unknown 5′ fusion partner genes and precise mapping of variable genomic breakpoints. Using a standardized bioinformatics algorithm, we identified kinase and cytokine receptor rearrangements in the majority of ALL patients with high burden of postinduction MRD and enrichment of IKZF1 mutation or deletion (IKZF1^del).