Haemopoietic stem cell transplantation for children in Australia and New Zealand, 1998–2006: a report on behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children’s Haematology Oncology Group

Every hospital in Australia and New Zealand that carries out HSCT contributes data to the ABMTRR. No remuneration is offered for participating in the data collection. Allogeneic and autologous HSCT procedures reported here were performed on children at the following centres: the Royal Children’s Hospital, Brisbane; Sydney Children’s Hospital; The Children’s Hospital at Westmead; the Royal Children’s Hospital, Melbourne; the Women’s and Children’s Hospital, Adelaide; Princess Margaret Hospital for Children, Perth; and Starship Children’s Hospital, Auckland. Activity figures for the Royal Children’s Hospital, Brisbane, include unrelated allogeneic HSCT procedures performed on patients under 16 years of age that were reported through the Royal Brisbane & Women’s Hospital.

Each treating centre seeks consent from patients or parents for the child’s clinical data to be transferred to the Registry. A single registration form is completed at each centre and sent to the Registry office when a transplant is performed. This contains the following information: coded patient and hospital identification, state and postcode of usual residence, sex, age, date of birth, transplant date, type of transplant, stem cell source, type of stem cell mobilisation, allogeneic donor details, disease diagnosis, and disease status at time of transplant.

The ABMTRR aims to capture all cases of HSCT in Australasia each year so that the data can be used for administrative and research purposes. The list of corresponding hospitals is regularly assessed for completeness by correspondence with leading transplant physicians. At the beginning of each calendar year, all of the hospitals are contacted to ensure they have supplied all registrations from the previous year. In the year 2001, an estimated 99.5% of all HSCT activity in the two countries was captured by the Registry.3

An annual follow-up request for all HSCT recipients recorded as alive is sent from the Registry to each contributing centre. The request asks for summary information on graft failure, persistent disease, relapse, new malignancy, death and cause of death. An annual data summary describing activity and outcomes is distributed to participating centres and associated researchers, usually within 12 months of the completion of a calendar year.

With the approval of the ABMTRR steering committee, we conducted a retrospective analysis of data on all transplants reported by paediatric hospitals to the ABMTRR over the 9-year period 1998–2006.

Transplant-related mortality (TRM) refers to deaths that occur as a direct consequence of the transplant procedure, such as organ toxicity from conditioning therapy, or complications such as infection in the setting of immunosuppression from treatment for GVHD. TRM, defined here as deaths from transplant-related causes within the first 100 days and within the first year after transplantation, was calculated by the method of cumulative incidence, considering relapse, persistence, or progression of the original disease as competing risks.4,5

An alternative donor is a non-HLA-matched sibling, other family member or unrelated donor.

Staged autologous transplants are planned multiple autologous transplants, including tandem transplants.

There was a non-significant reduction in TRM for allogeneic HSCT procedures between 1998–2001 and 2002–2006. For children undergoing HSCT from HLA-identical sibling donors, the cumulative incidence of TRM at 100 days after transplant was 6.8% in 1998–2001 compared with 5.1% in 2002–2006, while the 1-year TRM was 10.6% in 1998–2001 compared with 7.1% in 2002–2006 (Box 2). For children who received allogeneic transplants from alternative donors, the 100-day cumulative incidence of TRM was 16.5% in 1998–2001 compared with 11.7% in 2002–2006, while the 1-year TRM was 28.4% in 1998–2001 compared with 21.7% in 2002–2006 (Box 3). For children who had undergone autologous HSCT procedures, the 100-day cumulative incidence of TRM remained constant at about 3% between 1998 and 2006, while the 1-year TRM was 4.3% in 1998–2001 compared with 4.6% in 2002–2006 (Box 4).

The primary causes of death after HSCT for all patients are detailed in Box 5. The leading cause of death was persistence or relapse of the underlying disease, accounting for 28% of deaths within 100 days and 54% of deaths within 1 year of transplant. Other major causes of death within the first 100 days after transplant were veno-occlusive disease of the liver, infection, acute respiratory distress syndrome, multiple organ failure and GVHD.

Since 1998, there has been a steady increase in the use of umbilical cord blood for paediatric HSCT in Australasia (Box 6). The increased use of cord blood units has also resulted in a modest increase in HLA-mismatched transplants, from 17% in 2000 to 26% in 2006.

The growth of public banking of cord blood has led to a 32% increase in the number of children receiving unrelated HSCs from a donor sourced from the Australian Bone Marrow Donor Registry (Box 7). The number of bone marrow and peripheral blood stem cell donors sourced from the Australian Bone Marrow Donor Registry has remained relatively constant since 1998 (Box 8).

Characteristics of paediatric HSCT procedures conducted between 2002 and 2006 are detailed in Box 9. The median age of paediatric patients receiving a transplant during this period was 7 years (range, 0–19 years), with 61% of patients being male.

Allogeneic procedures accounted for 59% of HSCT activity. The most common indications for an allogeneic HSCT procedure were acute lymphoblastic leukaemia and acute myeloid leukaemia (Box 10). For allogeneic procedures (417 in total), the source of stem cells was marrow in 53%, peripheral blood stem cells in 17% and umbilical cord blood in 29%. Reduced-intensity (non-myeloablative) procedures accounted for only 6% of paediatric allogeneic HSCT procedures (Box 9).

Indications for autologous HSCT in Australian and New Zealand children from 2002 to 2006 are listed in Box 11. Autologous HSCT procedures were most commonly performed for solid tumours requiring very high-dose chemotherapy, such as neuroblastoma (23%), medulloblastoma (21%) and Ewing sarcoma (10%). Autologous HSCT for neuroblastoma was usually performed as a single myeloablative procedure, while HSCT for medulloblastoma and Ewing sarcoma/primitive neuroectodermal tumour (PNET) was most frequently given as staged reinfusions of stem cells following cycles of high-dose chemotherapy.