Successful engraftment and stable full donor chimerism after myeloablation with thiotepa, fludarabine, and melphalan and CD34‐selected peripheral allogeneic stem cell transplantation in hemophagocytic lymphohistiocytosis

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative option for primary hemophagocytic lymphohistiocytosis (HLH), a rare disease of infants and young children, characterized by recurrent fever, hepatosplenomegaly, and cytopenia. We report a case of successful engraftment and stable full-donor chimerism in a patient with HLH who underwent peripheral allogeneic CD34-selected HSCT. The donor was his 1-antigen-HLA-mismatched grandmother. After a conditioning regimen based on the combination of thiotepa, fludarabine, melphalan, and rabbit antilymphocyte serum, the patient received a megadose of 26.3 × 10 6 /kg of CD34 + peripheral blood cells. Neutrophil (>0.5 × 10 9 /L) and platelet (>50 × 10 9 /L) engraftment was observed on days +16 and +12, respectively, and the patient was discharged home on day +24. No acute or chronic GVHD was observed. Infectious complications were the main causes of re-hospitalization in the first year after transplantation, but no significant morbidity was observed thereafter. Thirty-two months after HSCT, the patient is alive and well, still in complete clinical remission of his underlying disease with a durable engraftment, normal NK activity and full donor chimerism. This case suggests that a fludarabine-based conditioning regimen and CD34-selected peripheral allogeneic HSCT may be a feasible option in case of unavailability of a fully HLA-matched related or unrelated donor. Am.

Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study

“…Various other groups have confirmed the feasibility and low toxicity of this RIC for allogeneic HSCT. [30][31][32][33] Consequently, the median age of the CD3/19 patients reported here is approximately a decade older than that previously reported in adult patients receiving haplo-HSCT with CD34 selected grafts. 5,34 The significant influence of graft composition and conditioning regimen on engraftment is illustrated by the fast engraftment kinetics observed.…”

Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP)

“…28,31 In order to diminish early organ toxicity, conditioning regimens with reduced extra-hematologic toxicity have been used without compromising engraftment. 16,27,36,37 In our cohort, a fludarabine-based conditioning regimen was used in 18% of HSCT, but we were unable to document that this had any significant influence on overall survival or TRM. Although promising, especially in non-malignant diseases, the use of regimens with reduced extramedullary toxicity requires further investigations in the future.…”

“…27 A severe humoral immunodeficiency requiring monthly immunoglobulin administration was diagnosed after 17 months, followed by bronchiectasis at +59 months.…”

Late cytomegalovirus polyradiculopathy following haploidentical CD34+-selected hematopoietic stem cell transplantation

“…(Fresenius, Graefeling, Germany) 20 mg/kg per day was administered from days À5 to À1, as described for haploidentical HSCT. 5 Both the donor and recipient were CMV seropositive (D þ /R þ ). CMV antigenemia was monitored weekly by pp65 antigen detection, as described previously.…”