What is the role of blood and marrow transplantation in pediatric acute myelocytic leukemia (AML) treatment?

Updated: Sep 12, 2017
  • Author: Mark E Weinblatt, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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A myeloablative combination of chemotherapy and irradiation followed by rescue with an infusion of HLA-matched stem cells to reconstitute the patient's bone marrow is an effective approach to cure acute myeloid leukemia. [15]

In several randomized studies, allogeneic transplantation raised overall and disease-free survival rates. [16]

However, this option is often not available, because HLA-matched donors are found for only approximately 25% of patients. In addition, for good-risk patients, transplantation is reserved for a second remission, because the salvage rate is quite high for such patients.

Options have nonetheless substantially increased with the availability of international HLA registries that can help in locating HLA-matched unrelated donors (MUD). Results with MUD are virtually equivalent to HLA-matched family donors.

Umbilical cord blood, which is rich in stem cells, has further expanded the availability of donor stem cells, because increased HLA mismatch appears to be better tolerated with such donor cells in terms of the development of high-grade graft versus host disease (GVHD).

In addition, the use of purged or unpurged autologous stem cells, which offer the advantages of availability and avoidance of graft versus host disease, are under investigation in clinical trials. However, to date, randomized studies in pediatric patients have not shown an overall survival advantage for autologous stem cell transplantation compared with chemotherapy.

Success rates for stem cell transplants have also increased because of improved GVHD prophylaxis and treatment, using different combinations of methotrexate, cyclosporine, tacrolimus, mycophenolate, and corticosteroids to lower mortality rates.

Hepatic veno-occlusive disease (also termed sinusoidal obstructive syndrome), a complication that can be fatal, has shown excellent responses to defibrotide. Defibrotide is a single-stranded polydeoxyribonucleotide derived from porcine tissue that possesses antithrombotic, thrombolytic, anti-inflammatory, and anti-ischemic properties.

In March 2016, the FDA approved defibrotide (Defitelio) for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT). Approval was based on findings of a phase 3 trial (n = 102) which observed significant improvement in survival and complete response with defibrotide 6.25 mg IV q6h compared to 32 historical controls. Survival at Day+100 post-HSCT was 38.2% in the defibrotide group and 25% in the control group (estimated difference of 230%; 95.1% confidence interval [CI] 5.2%-40.8%; P=.0109, using a propensity-adjusted analysis based on 4 prognostic factors of survival). Observed Day+100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% in the controls (19% difference using similar methodology; 95.1% CI 3.5-34.6; P=.0160). [17]

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