Die Behandlung der chronisch myeloischen Leukämie (CML) bei Kindern und Jugendlichen - Konzept der multizentrischen Pilotstudie CML-päd

Abstract

CML is a rare malignancy in childhood not yet being treated by an established protocol of the Society of Pediatric Oncology and Hematology (GPOH). Up to now only allogeneic bone marrow transplantation (BMT) offers a curative treatment option. After being enrolled into the study "CML-päd" patients with a matched sibling donor should undergo BMT within six months after diagnosis and within one year if an unrelated donor can be identified. Progress in palliative therapy results from the experience in adult patients: Hydroxyurea in combination with interferon alpha (IFN) is the treatment of choice. One aim of the study is to monitor quantitatively in bone marrow aspirates the activity of the disease in all patients on treatment every three months by performing cytogenetics and molecular analysis. As a pilot protocol intensification of treatment by idarubicine and cytarabine is scheduled one year after diagnosis for those patients not undergoing BMT and exhibiting after IFN treatment less than partial response. After progress to the accelerated phase of the disease a decision has to be made on an individual basis whether the patient should undergo new experimental treatment approaches.

Innovative approaches of targeted therapy for CML of childhood in combination with paediatric haematopoietic SCT

“…39 The prospective trial CML-paed I, running from 1995 to 2004, aimed to transplant children with CML in first CP after treatment with hydroxyurea±IFN from an HLA-matched family donor within 6 months and those with an unrelated donor within 12 months after diagnosis. 15,40 This approach resulted in an excellent probability of survival at 5 years of 87±11% (Figure 1) in the group grafted from HLA-identical family donors (n ¼ 41), but only 52 ± 9% if grafted from an HLAmatched unrelated donor (n ¼ 71) and 45±16% if grafted from an HLA-mismatched unrelated donor (n ¼ 36). The time interval from diagnosis to HSCT exerted a statistically insignificant influence on the outcome: the probability of survival for patients at 5 years transplanted HLA-fully matched in CP1 (n ¼ 144) was 74 ± 9%, if the procedure was performed within 6 months after diagnosis (n ¼ 49), and each 62±15% if performed after 6-12 months (n ¼ 52), or later than 12 months after diagnosis (n ¼ 43), Table 1 Risk-benefit considerations when balancing the use of short-term or long-term imatinib in childhood CML -Imatinib must currently be considered as the best upfront treatment for CML, a benefit that should be offered also to children.…”

Chronisch myeloproliferative Erkrankungen bei Kindern und Jugendlichen

“…Diese ist morphologisch und klinisch von einer akuten Leukämie nicht zu unterscheiden. Circa 30% der Blastenkrisen sind phänotypisch B-lymphoblastisch, die übrigen myeloblastisch oder myelomonozytär (30,32).…”

“…Die Symptome der CML in CP sind durch Medikamente relativ gut zu beeinflussen, ohne dass dadurch eine definitive Heilung erreicht wird. Letzteres gelingt nur durch die allogene Transplantation hämatopoetischer Stammzellen (7,9,16,32). Primäres Ziel der Therapie ist zunächst das Erreichen einer kompletten hämatologischen Remission; dies gelingt bei 90% der Patienten durch eine Monotherapie mit oral applizierbarem Hydroxyurea, womit die Leukozytenzahl auf niedrig-normale Werte eingestellt werden kann.…”