Factors influencing outcome and incidence of late complications in children who underwent allogeneic hematopoietic stem cell transplantation for hemoglobinopathy

Pediatr Hematol Oncol. 2012 Nov;29(8):694-703. doi: 10.3109/08880018.2012.725198. Epub 2012 Sep 28.

Abstract

Background: Hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for severe hemoglobinopathy (HGP). Late complications (LCs) are all events occurring beyond two years post-HSCT. We retrospectively analyzed prevalence, factors influencing occurrence, and prognosis of LCs post-HSCT for HGP.

Patients and methods: Between 2000 and 2011, 47 patients (21 males, 26 females; 43 with beta thalassemia major, four with sickle cell disease) who had survived more than two years post-HSCT for HGP were retrospectively reviewed. Mean age at HSCT was 7.7 years (1.1-32 years); mean follow-up was 7.1 years (2-11.6 years); 11 patients were splenectomized; mean ferritin level was 3022 ng/mL (350-10900); and seven patients underwent a second HSCT.

Results: Endocrinological complications were observed with primary gonadal failure in 16/20 mature females and 4/11 mature males, in five patients with primary hypothyroidism and in four with insulin-dependent diabetes mellitus (DM). Skeletal complications were observed in 10 with secondary osteoporosis; 22 patients had elevated transaminase levels; two had hepatitis B reactivation. Neurological, cardiac and ocular manifestations were relatively rare. A higher incidence of LCs was observed in splenectomized than in nonsplenectomized patients: cGVHD -64% versus 13% (P = .003); endocrine abnormalities -91% versus 30.5%, (P = .001); elevated transaminase levels -73% versus 33% (P = .043); mortality -18% versus 2.7% (NS).

Conclusions: LCs post-HSCT for HGP are common and heterogeneous. Etiology is multifactorial with iron overload (IO), class, splenectomy, age, chronic GVHD, and corticosteroid (CS) treatment. Our data may help build follow-up guidelines to limit, detect, and treat any LCs and improve quality of life.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / epidemiology
  • Anemia, Sickle Cell / therapy
  • Child
  • Child, Preschool
  • Chronic Disease
  • Endocrine System Diseases / blood
  • Endocrine System Diseases / epidemiology*
  • Endocrine System Diseases / etiology
  • Eye Diseases / blood
  • Eye Diseases / epidemiology*
  • Eye Diseases / etiology
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / epidemiology*
  • Graft vs Host Disease / etiology
  • Heart Diseases / blood
  • Heart Diseases / epidemiology*
  • Heart Diseases / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hepatitis B / blood
  • Hepatitis B / epidemiology*
  • Hepatitis B / etiology
  • Humans
  • Incidence
  • Infant
  • Male
  • Nervous System Diseases / blood
  • Nervous System Diseases / epidemiology*
  • Nervous System Diseases / etiology
  • Retrospective Studies
  • Risk Factors
  • Transplantation, Homologous
  • beta-Thalassemia / epidemiology
  • beta-Thalassemia / therapy