Minimal disseminated and residual disease (MDD/MRD) analyzed by qualitative PCR for NPM-ALK fusion transcripts are validated prognostic factors in pediatric ALK-positive anaplastic large cell lymphoma (ALCL). Although potentially promising, MDD quantification by quantitative real-time PCR in international trials is technically challenging. Quantification of early MRD might further improve risk stratification. We aimed to assess droplet digital PCR for quantification of minimal disease in an inter-laboratory setting in a large cohort of 208 uniformly treated ALCL patients. Inter-laboratory quality control showed high concordance. Using a previously described cut-off of 30 copies NPM-ALK/10⁴ copies ABL1 (NCN) in bone marrow and peripheral blood, MDD quantification allowed identification of very high-risk patients (5-year PFS% 34 ± 5 for patients with ≥30 NCN compared to 74 ± 6 and 76 ± 5 for patients with negative or <30 NCN, respectively, p < 0.0001). While MRD positivity was confirmed as a prognostic marker for the detection of very high-risk patients in this large study, quantification of MRD fusion transcripts did not improve stratification. PFS% was 80 ± 5 and 73 ± 6 for MDD- and MRD-negative patients, respectively, versus 35 ± 10 and 16 ± 8 for MRD-positive patients with <30 and ≥30 NCN, p < 0.0001. Our results suggest that MDD quantification by dPCR enables improved patient stratification in international clinical studies and patient selection for early clinical trials already at diagnosis.

Background: Rising survival rates have created a growing population of childhood cancer survivors (CCSs) who have an increased risk of late effects and require long-term follow-up (LTFU) care. Existing services are often fragmented and may not reflect survivors’ priorities; optimizing such care requires understanding not only the self-reported burden of late effects and their impact on daily lives but also survivors’ information status and their preferences for future care. Methods: Survivor Deutschland e.V. conducted a nationwide cross-sectional online survey assessing the current late effects, daily-life impairments, subjective information statuses, current follow-up structures, and preferences for future LTFU care. A total of 339 CCSs were included, covering all childhood cancer entities, most frequently leukemia (30.7%), central nervous system tumors (18.3%), and lymphoma (16.5%). Data were analyzed descriptively and supplemented by paired non-parametric analyses. Results: Overall, 74.3% (252/339) reported at least one late effect. Self-rated limitations in daily life had a median of five (Q1–Q3 3–7) on a 1–10 scale, which increased with the number of reported late effects. The most frequently affected domains were endocrine (36.3%, n = 123), fertility (33.6%), psychological (30.4%, n = 103), neurocognitive (26.0%, n = 88), and orthopedic (24.8%, n = 84) problems. A majority (69.3%, n = 235) knew that late effects existed yet felt insufficiently informed, and 4.4% only learned of these through the survey. Among 172 survivors in adult follow-up care, only 26.8% (46/172) reported access to structured, specialized LTFU care, whereas 56.4% (97/172) preferred this model. Survivors rated the importance of LTFU care highly (median 9/10) but rated satisfaction with their current care as much lower (median 3/10). The most valued components were the coverage of follow-up costs, sufficient consultation time, a dedicated contact person, and clear communication of results. Psychological support was a notable gap (5.8%, 10/172 current access vs. 17.9% 31/172 preferred), and 84.1% were willing to travel up to two hours or more for high-quality care. Conclusions: German CCSs report a high late-effect burden, meaningful impairment of their daily lives, a pronounced information gap, and substantial unmet care needs. These patient-centered findings support structured, risk-adapted LTFU with proactive information, integrated psychological support, and sustainable financing at specialized LTFU centers.