Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency.

Genetic mutations of proteins regulating nuclear factor of kappa-light polypeptide gene enhancer in B lymphocyte (NF-kappaB) activation result in heritable diseases of development and immunity. Hypomorphic, X-linked mutations in the IKBKG gene (NF-kappaB essential modulator (NEMO) protein), and hypermorphic, autosomal dominant mutations in the IKBA gene (inhibitor of NF-kappaB (IkappaB)-alpha protein), are associated with a phenotype of immune deficiency and often ectodermal dysplasia (ED-ID). ED-ID predisposes patients to recurrent and life-threatening infections and is typically fatal within the first few years of life. Allogeneic hematopoietic SCT (HSCT) may correct the immune deficiency associated with NEMO or IkappaBalpha mutations, but there is very little published data. We gathered clinical data on three ED-ID patients that had undergone HSCT. Conditioning regimens were variable, as were the stem cell sources. All three patients experienced engraftment difficulties as well as post transplant complications. These cases suggest that patients with immune deficiencies caused by NEMO or IkappaBalpha mutations may have intrinsic barriers to successful engraftment, which require further investigation.

Stem cell transplantation for neuroblastoma.

High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to SCT and supportive care, most notably the transition to PBSC, have resulted in further improvement in survival and decreases in treatment-related mortality. Research into experimental approaches to hematopoietic SCT is ongoing.