Cytosine Arabinoside and Mitoxantrone Followed by Second Allogeneic Transplant for the Treatment of Children With Refractory Juvenile Myelomonocytic Leukemia

Abstract

Summary Hematopoietic stem cell transplantation (HSCT) remains the only curative option for most patients with juvenile myelomonocytic leukemia (JMML). However, persistent disease and relapse rates after transplant range from 26% to 58%. We report the successful use of second HSCT after preparation with mitoxantrone and cytosine arabinoside (Ara-C) for patients with refractory or recurrent disease. Between 1993 and 2006, 5 children who underwent HSCT at our institution as initial therapy for JMML had persistent disease or relapsed. Pre-HSCT conditioning varied and donors were either HLA-matched siblings (n = 2) or matched unrelated donors (n = 3). After initial HSCT, they subsequently received high-dose Ara-C (3 g/m2 IV) every 12 hours on days −8 through −3 and mitoxantrone (10 mg/m2/d IV) on days − 8, − 7, − 6 followed by second HSCT from their original donors. All 5 patients are alive at 88, 179, 199, 234, and 246 months with no evidence of JMML, no significant toxicity, and 100% donor chimera as determined by PCR short-tandem repeat analysis. Our experience supports second transplant utilizing high-dose Ara-C and mitoxantrone in children with JMML who do not respond or relapse after first transplant.

Long-Term Survival and Late Effects among One-Year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

“…(1, 2, 9–15) Studies of second transplant in children have demonstrated more favorable survival, but are limited by small patient numbers. (11, 16) Previous studies of second transplant have been limited in sample size and hence, have been inconsistent in identifying favorable factors for longer survival following second allogeneic HCT. Notwithstanding the limitation of small sample size, factors associated with superior survival include younger recipient age, longer duration of remission between transplants, complete remission (CR) at second transplant, bone marrow as the stem cell source, the use of a fully HLA-matched donor, the presence of acute and chronic graft-versus-host disease (GVHD), and transplantation from a female donor.…”

Role of Second Transplantation for Children With Acute Myeloid Leukemia Following Posttransplantation Relapse

“…In the present era, with several advances in posttransplantation supportive care practices, it is not unusual for a second allogeneic HSCT to be a considered as treatment for patients whose disease relapse after first HSCT; however, few reports had been published focusing its efficacy and safety . Our current study is one of the largest reports in the pediatric population and demonstrated that more than 40% of the children can be cured following a second HSCT and second remission.…”

“…a second allogeneic HSCT to be a considered as treatment for patients whose disease relapse after first HSCT; however, few reports had been published focusing its efficacy and safety. [2][3][4][5][6][7][8] Our current study is one of the largest reports in the pediatric population and demonstrated that more than 40% of the children can be cured following a second HSCT and second remission. A major concern of HSCT for the second time is the potentially high risk of transplant-related toxicity, and indeed, an extremely high rate of transplant-related mortalities (TRM) was the major cause of treatment failure in the previous reports.…”

“…Because of recent advances in chemotherapy and better risk stratification using various prognostic factors for pediatric acute myeloid leukemia (AML), hematopoietic stem cell transplantation (HSCT) in those patients who achieve a first remission is restricted to patients with a relatively high risk of relapse . Second HSCT is a potentially curative option; however, few reports have been published on this topic, and its efficacy and feasibility are not clear . In this study, children with AML (younger than 18 years at initial diagnosis), who underwent a second allogeneic HSCT in second remission, were analyzed retrospectively using the database provided by the Japanese Society of Hematopoietic Cell Transplantation (JSHCT) registry.…”

“…[1] Second HSCT is a potentially curative option; however, few reports have been published on this topic, and its efficacy and feasibility are not clear. [2][3][4][5][6][7][8] In this study, children with AML (younger than 18 years at initial diagnosis), who underwent a second allogeneic HSCT in second remission, were analyzed retrospectively using the database provided by the Japanese Society of Hematopoietic Cell Transplantation (JSHCT) registry.…”