Allogeneic hematopoietic stem cell transplantation for infants with idiopathic myelofibrosis

Abstract

IMF is a rare disease in children that can present during infancy and has a protracted course. The only known curative approach for this disease in adult patients is allogeneic HSCT. There are very few reports describing the long-term outcome of young children following stem cell transplantation for IMF. We report on eight patients less than two yr of age with IMF that did not resolve with supportive care measures. All patients underwent myeloablative conditioning regimen with busulfan and cyclophosphamide ± ATG followed by HSCT from matched related (n = 6) or unrelated donor (n = 2). All patients achieved neutrophil and platelet engraftment. Four patients had grade II-III acute GVHD, and chronic GVHD developed in five patients (three mild and two severe). At a median follow-up of eight and a half yr (0.7-9), all patients are alive with complete resolution of their hematologic manifestations. At the last follow-up, all patients had normal endocrine function except for one patient who developed hypothyroidism. To date, this is the largest cohort of young children with IMF treated successfully with HSCT, with the longest duration of follow-up. In conclusion, our study showed that HSCT is a curative option for infants with IMF.

Single Daily Busulfan Dosing for Infants with Nonmalignant Diseases Undergoing Reduced-Intensity Conditioning for Allogeneic Hematopoietic Progenitor Cell Transplantation

“…Similarly, only 1 of our patients developed seizure, likely caused by cyclosporine toxicity, which is in line with the low risk of Bu-induced seizure reported in children [40]. The rate of acute or chronic GVHD development was also very low in our study, in contrast to other studies of infants who underwent HPCT [41]. This low GVHD rate could be related to the decreased inflammatory stimuli associated with our RIC regimen, which avoided triggering excessive cytokine release [42].…”

Myeloproliferative neoplasms in children

“…Neutropenia is less common and observed in approximately one-third of patients[17]. Studies on precise laboratory values at presentation of pediatric PMF are not available, but the available case reports suggest Hgb and platelet values in the range of 4.9–9.4 g/dL and 23–242 ×10 9 /L respectively[30]. Other laboratory values commonly increased in adult PMF patients – including LDH, bilirubin and uric acid levels suggesting high marrow cell turnover – are not well documented in children.…”

“…Outcomes after HSCT are reported in single or small case series reports with heterogeneous donors, stem cell sources and conditioning regimens[10, 17, 21, 30, 51, 62, 64–66, 71]. Almost all reported cases are those of young children (<3 years) and infants.…”

Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis

“…PMF is frequently observed prior to the onset of other diseases such as acute myeloid leukemia (AML) [4], [5]. Effective approaches for the treatment of this disease include allogeneic hematopoietic stem cell transplantation (HSCT) [6] and splenectomy [7]. The incidence of PMF is approximately 1 case per 100,000 people, with a median age of onset of 60 years [8].…”

“…The incidence of PMF is approximately 1 case per 100,000 people, with a median age of onset of 60 years [8]. PMF is extremely rare in children [9], although sporadic childhood PMF cases have been described throughout the world [2], [6], [10]. Up till now, most studies have focused more on the clinical and cytogenetic phenotypes associated with the disease, rather than on drug therapies and related mechanisms.…”