Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen

Abstract

Summary:The histiocytoses are rare disorders of antigen-processing phagocytic or antigen-presenting cells. Allogeneic bone marrow transplantation (BMT) can be curative of these disorders. We report a series of five children with Langerhans cell histiocytosis (n ¼ 2) or hemophagocytic lymphohistiocytosis (n ¼ 3), who received allogeneic BMT with a total body irradiation (TBI)-containing regimen (TBI, cytarabine, and cyclophosphamide) at our institution between 1995 and 2000. One of these patients received busulfan, cyclophosphamide, and etoposide for the first of two BMTs. All grafts except one (a matched sibling-donor graft) were T-cell-depleted grafts from unrelated donors. All received cyclosporine graft-versushost disease (GvHD) prophylaxis; the recipient of the matched sibling graft also received methotrexate. Three patients engrafted at a median of 24 days after transplantation. The patient who did not receive TBI experienced primary graft failure and recurrent disease. After the TBI-containing conditioning regimen was given, a second transplant engrafted on day +17. One patient with concurrent myelodysplastic syndrome died of toxicity on day +33 without evidence of engraftment. No acute or chronic GvHD was observed. Four patients survive disease-free, a median of 63 months after transplantation, all with Lansky performance scores of 100. We conclude that a conditioning regimen containing TBI but not etoposide is effective in allogeneic BMT for children with histiocytic diseases. Bone Marrow Transplantation (2003) 31, 981-986.

Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning

“…Subsequently, a few cases of allogeneic SCT in LCH patients failing other therapeutic approaches have been published. [10][11][12][13][14][15][16][17][18][19][20][21] In order to critically evaluate the published data on myeloablative allogeneic SCT, we exclusively reviewed publications concerning pediatric LCH patients with involvement of risk organs prior to SCT (Table 4). In all, 29 pediatric patients underwent myeloablative allogeneic SCT for LCH with risk organ involvement.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21] However, myeloablative high-dose regimens are associated with a high treatment-related morbidity and mortality, especially in severely ill LCH patients. For children with other nonmalignant diseases who are not eligible for conventional myeloablative conditioning regimens, the use of reduced-intensity conditioning regimens is feasible and associated with stable engraftment and cure from the underlying disease in many cases.…”

Solid tumors in children

“…120,121 Four of fi ve patients who received autologous HSCT had persistent active disease after transplantation. Allogeneic HSCT has been used for a small number of patients with unresponsive disease; 13 out of 22 children remained alive at the time of reporting.…”

Autologous stem cell transplantation for refractory Langerhans' cell histiocytosis

“…4 In addition, in most of the pediatric patients, myeloablative high-dose regimens are associated with a high treatmentrelated morbidity and mortality, and mobilizing stem cells from pediatric patients may be difficult. 4,9 In our patient, some risk factors for LCH resolved after aPBSCT and she maintained complete remission for 10 months, having never previously experienced such a stable period. Thus, aPBSCT performed for LCH can be considered as a second treatment choice for patients with no acceptable donor.…”

“…7,8 In particular, the successful allogeneic BMT performed by Ringden et al 8 casts new light on LCH patients failing other therapeutic approaches. 5,8,9 In contrast, autologous marrow rescue has been considered a less attractive option due to the inherent tendency of the marrow to give rise to LCH. However, a case of effective autologous BMT for LCH is also reported, although it is a rare case.…”