Growth and Development After Hematopoietic Cell Transplantation

Summary:It is generally assumed that busulphan/cyclophoshamide (Bu/Cy)-based conditioning regimens for haematopoietic stem cell transplantation (SCT) do not affect growth. We evaluated growth and endocrine function after Bu/Cybased conditioning in 64 children without a history of irradiation. Mean height standard deviation scores remained stable, but unexplained disturbances of growth after SCT were found in 17/48 (35%) of the children without growth-limiting disorders (10/23 in patients treated for haematological malignancies). In 10 patients, growth hormone (GH) secretion status was evaluated, and insufficient GH secretion was diagnosed in four patients. Thyroid function was evaluable in 52 patients. Two developed antibody-mediated thyroid disorders and 10 (19%) compensated primary hypothyroidism. Gonadal function was evaluable in 21 patients and was normal in all seven patients treated with low-dose Bu (8 mg/kg), whereas seven of the 14 children receiving high-dose Bu (16-20 mg/kg) developed gonadal failure; the majority of these patients had not been exposed to gonadotoxic therapy prior to Bu/Cy. Of the 49 evaluable patients, 16 developed subclinical hyperparathyroidism. We conclude that, besides gonadal and thyroid dysfunction, impaired growth and hyperparathyroidism often occur after Bu/Cy conditioning for SCT and that growth impairment may be the result of insufficient GH secretion.

Section: Discussionmentioning

confidence: 99%

“…23 Recovery of gonadal function, although rare, has been documented in both sexes. 22 Patients should be aware of the possibility of premature ovarian failure as well as recovery of gonadal function, in view of contraceptive measures and family planning. Hyperparathyroidism was found in 35% of our evaluable patients.…”

Section: Discussionmentioning

confidence: 99%

Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood

Bakker

Oostdijk

Bresters

et al. 2004

“…38 Annual evaluation included measurement of growth hormone (GH), thyroxine (T4) and thyroid-stimulating hormone (TSH) and measurements of engraftment. 39 …”

Section: Follow-up and Quality Of Lifementioning

confidence: 99%

Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience

Yusuf

Frangoul

Gooley

et al. 2004

Summary:The purpose of this study was to evaluate the role of allogeneic bone marrow transplantation (BMT) in children with myelodysplastic syndrome (MDS). In total, 94 consecutive pediatric patients with MDS received an allogeneic BMT from 1976 to 2001 for refractory anemia (RA) (n ¼ 25), RA with ringed sideroblasts (RARS) (n ¼ 2), RA with excess blasts (RAEB) (n ¼ 20), RAEB in transformation (RAEB-T) (n ¼ 14), juvenile myelomonocytic leukemia (JMML) (n ¼ 32) or chronic myelomonocytic leukemia (CMML) (n ¼ 1). The estimated 3-year probabilities of survival, event-free survival (EFS), nonrelapse mortality and relapse were 50, 41, 28 and 29%, respectively. Patients with RA/RARS had an estimated 3-year survival of 74% compared to 68% in those with RAEB and 33% in patients with JMML/CMML. In multivariable analysis, patients with RAEB-T or JMML were 3.9 and 3.7 times more likely to die compared to those with RA/RARS and RAEB (P ¼ 0.005 and 0.004, respectively). Patients with RAEB-T were 5.5 times more likely to relapse (P ¼ 0.01). The median follow-up among the 43 surviving patients is 10 years (range 1-25). We conclude that allogeneic BMT for children with MDS is well tolerated and can be curative.

“…Patients were eligible for the study if all of the following criteria were present: (1) a PID treatable with HCT; (2) factor(s) that would increase the risk of early transplant-related mortality (TRM, death before day 100) following conventional HCT; and (3) identification of a related or unrelated donor matched for HLA-A, -B, -C, -DRB1 and -DQB1 alleles. Factors considered to increase the risk of mortality included: (1) infection-defined as fungal or viral infections involving one or more organs present at time of transplant or a life-threatening opportunistic infection diagnosed within 3 months of HCT; (2) organ dysfunction-defined as any of the following: liver dysfunction (transaminase 43 times the upper limit of normal), renal dysfunction (biopsy-proven renal disease or glomerular filtration rate o50%), cardiac dysfunction (cardiac ejection fraction o40%), or pulmonary dysfunction (diffusing capacity of the lung for carbon monoxide of o60%); (3) older age (45 years)-applicable only in cases for which previous studies have documented age to be associated with higher risk of TRM; 10,11 (4) unrelated donor (URD)-applicable only in disorders for which previous studies have documented disease-free survival of o50% or if the reported experience has not been sufficient to justify a conventional URD HCT. 10 Excluded from this analysis were patients with severe combined immunodeficiency disorder who received grafts from HLA-matched related donors (n ¼ 1).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, children treated with myeloablative regimens often suffer late effects such as infertility, hormonal dysfunction, growth failure and secondary malignancies. [1][2][3][4] Certain factors, including older age and coexisting chronic infections or organ dysfunction, confer greater risks for toxicity or death following myeloablative conditioning regimens.…”

Section: Introductionmentioning

confidence: 99%

Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders

Burroughs

Storb

Leisenring

et al. 2007

This study was designed to determine the safety of a nonmyeloablative regimen in patients with primary immunodeficiency disorders (PID) who had infections, organ dysfunction or other risk factors that precluded conventional hematopoietic cell (HC) transplant. Fourteen patients received HLA-matched related (n ¼ 6) or unrelated (n ¼ 8) HC grafts from marrow (n ¼ 8), peripheral blood mononuclear cells (n ¼ 5) or umbilical cord blood (n ¼ 1), either without conditioning (n ¼ 1), or after 200 cGy total body irradiation alone (n ¼ 3) or with 90 mg/m 2 fludarabine (n ¼ 10). All patients were given postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Mixed (n ¼ 5) or full (n ¼ 8) donor chimerism was established in 13 patients, and one patient rejected the graft. Eight patients developed acute grade III (n ¼ 1) and/or extensive chronic GVHD (n ¼ 8). With a median follow-up of 4.9 (range, 0.7-8.1) years, the 3-year overall survival, event-free survival and transplant-related mortality were 62, 62 and 23%, respectively. Correction of immune dysfunction was documented in 8 of 10 patients with stable donor engraftment. These preliminary results indicated that this approach was associated with stable donor engraftment and a low incidence of early mortality and, thus, can be considered for certain high-risk patients with PID. However, there was a risk of GVHD, which is an undesirable outcome for this group of patients.