Allogeneic Stem Cell Transplantation for Pediatric and Adolescent Patients with CML: Results from the Prospective Trial CML-paed I

Abstract

Purpose: Stem cell transplantation (SCT) can definitely cure chronic myeloid leukemia (CML), a rare disease in childhood. We prospectively evaluated the results of early SCT in pediatric CML after standardized pretreatment with hydroxyurea±interferon.

Patients and Methods: Between 1995 and 2004, 200 children (median age: 12.4 years) were enrolled and stratified: given the availability of an HLA-matched related donor (MRD), SCT was scheduled within 6 months and otherwise from an unrelated donor (UD) within 12 months following diagnosis.

Results: 176 patients underwent SCT; from MRD within median 4 months and from UD within median 11 months after diagnosis. At SCT, 158 patients were in chronic phase (CP1 or CP2), 9 patients were in accelerated phase and 9 patients were in blast crisis (BC). The conditioning regimen – total body irradiation or busulfan – exerted no different impact on overall survival (OS). Probability of OS at 5 years was 87±11% if grafted from a sibling (n=41), 52±9% from matched UD (MUD, n=71), and 45±16% from mismatched donors (MMD, n=55), respectively. A trend for better OS in CP1 was observed if SCT was performed within 6 months (n=49; 74±9%), compared to 7–12 months (n=52; 62±15%), and >12 months (n=43; 62±17%) after diagnosis, respectively (p=0.157). Probability of relapse at 5 years was 20±12%. Transplant-related mortality and graft-versus-host disease mainly contributed to the inferior outcome in UD and HLA-mismatched SCT.

Conclusion: These data from the first prospective trial on CML restricted to children and adolescents might be considered for decision making when balancing the risks of SCT against the increasing use of imatinib as upfront treatment for CML.

Zusammenfassung

Hintergrund: Die allogene Stammzelltransplantation (SZT) ist kurativ für Patienten mit CML, einer im Kindesalter seltenen Leukämie. Wir evaluierten prospektiv den Effekt einer frühzeitigen SZT nach standardisierter Vorbehandlung mit Hydroxyurea±Interferon bei pädiatrischer CML.

Patienten und Methoden: Zwischen 1995 und 2004 wurden 200 Kinder und Jugendliche (medianes Alter: 12,4 Jahre) eingeschlossen: Bei HLA-kompatiblem verwandtem Spender (MRD) wurde die SZT binnen 6 Monaten angestrebt; bei unverwandten Spendern (UD) binnen 12 Monaten.

Ergebnisse: 176 Patienten wurden transplantiert; mit einem MRD im Median nach 4 Monaten und mit einem UD binnen 11 Monaten nach Diagnose. Bei SZT befanden sich 158 Patienten in chronischer Phase (CP1/CP2), 9 in Akzeleration und 9 in Blastenkrise. Die Konditionierung – Ganzkörperbestrahlung oder Busulfan-basiert – hatte keinen Einfluss auf die Überlebenswahrscheinlichkeit. Diese betrug nach 5 Jahren mit einem Geschwisterspender (n=41) 87±11%, mit MUD (n=71) 52±9% und mit nicht HLA-kompatiblem Spender (MMD, n=55) 45±16%. Patienten in CP1 mit SZT binnen 6 Monaten zeigten trendmäßig eine höhere Überlebenswahrscheinlichkeit (n=49; 74±9%) als jene, die nach 7–12 Monaten (n=52; 62±15%) oder >12 Monaten (n=43; 62±17%) transplantiert wurden (p=0,157). Die Rezidivwahrscheinlichkeit nach 5 Jahren betrug 20±12%. UD und MMD waren mit höherer Transplantat-gegen-Wirt-Erkrankung und therapiebedingter Mortalität assoziiert.

Schlußfolgerung: Diese Daten der ersten prospektiven Studie zur CML im Kindes- und Jugendalter können zur Entscheidungsfindung herangezogen werden, wenn die Risiken einer SZT gegen die zunehmend eingesetzte Primärtherapie mit Imatinib abzuwägen sind.

Key words

Chronic myeloid leukemia - children - adolescents - stem cell transplantation

Schlüsselwörter

Chronisch myeloische Leukämie - Kinder - Adoleszente - Stammzelltransplantation

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