The COG and CCLG guidelines are designed to comprehensively address all modalities of cancer therapy and recognize differences in late effects noted based upon therapeutic technique, treatment era, dose, and developmental stage in children. They are very straightforward for children who receive a small number of agents followed by local surgery or radiation. The major challenge with applying these guidelines to the pediatric HCT population is that the majority of patients undergoing HCT have been treated with a large number of agents both prior to and after a first relapse and sometimes subsequent relapses. This may mean that risk of worsening organ damage with the megadose therapy of HCT is higher in some children due to pre-existing treatments, therefore, listing effects due to a single agent does not do justice to the total effect of an HCT regimen. Furthermore, over time, the ability to delivery HCT safely to higher risk children who have received more regimens and potentially multiple transplants has increased. Thus, adverse effects of HCT are expected to be worse in these heavily pre-treated children. In addition, genetics, age, gender, lifestyle, and existent comorbidities can have an effect. Finally, transplant-specific effects such as altered immunity and GVHD along with prolonged exposure to immune suppressive agents significantly changes patients’ long-term risk profiles (i.e. prolonged prednisone exposure dramatically affects growth and bone health, prolonged intense immune suppression affects second malignancy risk, etc.: ). While the COG and CCLG guidelines partially address some of these issues in their HCT-specific sections, the complexity of the problem makes addressing these issues in a comprehensive way challenging.
Figure 1 Late effects after HCT are a result of the interaction between pre-HCT exposures to chemotherapy, radiation, and surgery with the transplant conditioning regimen and acute transplant complications and finally with transplant specific complications such (more ...)
A further practical challenge with using the COG guidelines for transplant-specific late effects is that they are very difficult to glean from this enormous work. For example, challenges post-HCT patients experience with growth failure are spread out amongst the many therapeutic exposures that pre-HCT patients have, and the task of pulling things together for these very complex patients is daunting. Finally, the COG and CCLG guidelines are strongly oriented toward children with cancer. More than a third of pediatric HCT patients undergo the procedure due to non-malignant indications.
The CIBMTR/ASBMT/EBMT/APBMT/BMTSANZ/EMBMT/SBTMO guidelines (hereafter called “joint transplant society guidelines”) approach the subject in a very practical, although less comprehensive fashion. Broad guidelines applicable to the most common late effects noted after HCT are included. Specific types and timing of follow up are outlined and a large number of transplant-specific references are included. It is easier for both patients and practitioners to look at these guidelines and know the major issues that should be covered in a follow up visit of a patient who has undergone HCT. Caveats include the fact that the guidelines do not address the many differences in outcomes that can occur after HCT based upon pre-HCT therapies and comorbidities. In addition, the simplicity offered by these general guidelines does not allow one to look at differences in degree of intensity of preparative regimens used, extent of GVHD and post-HCT immune suppression undergone, different outcomes based upon use of different stem cell sources, and risks based upon age, specific non-malignant disorder of the recipient, etc..
With the strengths and weaknesses of the published recommendations in mind, offers a comparison between COG, Joint Transplant Society, and CCLG recommendations for specific areas. also includes specific recommendations from our panel of experts based upon updated evidence. There are many areas that are not addressed in this table that would need to be included in comprehensive guidelines (screening for second malignancies, neurocognitive, functional and quality of life effects, consequences of prolonged immune deficiency, etc.).
Selected Screening Recommendations for Late Effects After HCT in Pediatric Patients