Marrow transplant experience in children with acute lymphoblastic leukemia: An analysis of factors associated with survival, relapse, and graft‐versus‐host disease

Abstract

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.

Isolated testicular relapse after bone marrow transplant with total body irradiation and testicular boost in acute lymphoblastic leukemia

“…Chronic GVHD has been shown to be associated with a lower risk of marrow relapse after transplant. 5 Our patient had chronic GVHD and the bone marrow remained in continuous remission after BMT. The graftversus-leukemia effect associated with GVHD may protect the child from marrow relapse.…”

“…The sites of relapse are mainly bone marrow or bone marrow combined with extramedullary organs. 2,5 Isolated extramedullary relapse after transplant is less common. In the early 1980s, some series reported a high incidence of isolated testicular relapse in up to 25% of boys, despite total body irradiation from 12 to 15.75 Gy.…”

“…In the early 1980s, some series reported a high incidence of isolated testicular relapse in up to 25% of boys, despite total body irradiation from 12 to 15.75 Gy. 5,6 Some centers advocated pretransplant testicular biopsy, 7 but this was not widely practiced due to poor predictive value. Most centers now adopt the approach of booster testicular radiotherapy in addition to TBI.…”

“…Most centers now adopt the approach of booster testicular radiotherapy in addition to TBI. 2,3,5 A total radiation dose of 18 Gy to the testes is usually delivered when TBI is employed as part of the conditioning regimen for BMT in ALL patients. This 18 Gy dosage was based on effective CNS control with prophylactic cranial irradiation.…”

“…Even though there has been a report of long-term survival after local treatment to the testes without systemic chemotherapy, numbers are too small to permit this to be the recommended treatment. 5 Systemic chemotherapy with high-dose methotrexate, without testicular radiotherapy, has recently been shown to be effective in treatment of testicular relapse. 10 However, posttransplant patients usually do not tolerate high-dose chemotherapy well which might hinder the deliverance of highdose chemotherapy.…”