Late effects after Chemotherapy versus Allogeneic Stem Cell Transplantation in Childhood Relapsed Acute Lymphoblastic Leukemia – A report from the ALL-REZ BFM Study Group

To assess late effects in patients with relapsed ALL after chemotherapy versus allogeneic stem cell transplantation (SCT) we initiated an analysis on children diagnosed with acute lymphoblastic leukemia (ALL) in 2nd complete continuous remission (CCR) for more than 2 years previously treated according to ALL REZ BFM trials 1983–1996.

Patients were selected by a matched cohort design with match parameters considered most relevant for the development of specific late effects. A standardized questionnaire for retrospective evaluation of late effects was sent to 57 clinical centers in Germany, Austria and Switzerland.

48 patients having received chemotherapy were matched to 48 patients having received SCT. The matched patient characteristics (sex, age, site of relapse, duration of CR after relapse and observation time) showed identical distribution in the two groups whereas time point, immunophenotype of relapse and consequently the risk groups S2 to S4 were differently distributed with an overrepresentation of high risk patients in the SCT group.

As a major factor for the development of late effects we found active chronic graft versus host disease (cGVHD) in 9 out of 48 patients (18%) in the SCT group whereas 9 other patients were recovered from cGVHD.

There were no significant differences concerning general status, occurrence of infections, neurological status, heart and circulation, audiological capacity, renal and liver and gastrointestinal function.

However, we found significantly more patients after SCT with growth/weight deviation and more patients with a delay in sexual development leading to a higher need for hormonal substitution. Ophthalmological problems, pulmonary dysfunction, skin disorders, movement deficencies due to joint retractions and an impaired dental status were found in significantly more SCT patients.

The validity of the study might be affected by a comparably low patient number and missing values in some parameters. The retrospective evaluation of late effects might have caused a bias due to an overreport of patients with severe clinical problems.

Nevertheless, and as expected we found a significantly higher rate of late effects in variety of compartments and organs after SCT.

We conclude that allogeneic SCT should only be considered in patients with a proven significant benefit with respect to overall survival and suggest future prospective evaluation of late effects in patients after chemotherapy and SCT.