Hematopoietic stem cell transplantation in severe congenital neutropenia

Carlsson, Göran; Winiarski, Jacek; Ljungman, Per; Ringdén, Olle; Mattsson, Jonas; Nordenskjöld, Magnus; Touw, Ivo P.; Henter, Jan‐Inge; Palmblad, Jan; Fadeel, Bengt; Hägglund, Hans

doi:10.1002/pbc.22836

Cited by 37 publications

(31 citation statements)

References 39 publications

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“…There are currently 18 published reports of HCT in patients with SCN for a total of 65 patients transplanted without malignant transformation (Tables 1 and 2)[8 ⍰ , 40, 41 ⍰ , 42 ⍰ , 43–51, 52 ⍰ , 53, 54] and 18 patients transplanted with development of MDS or leukemia (Table 3)[8 ⍰ , 41 ⍰ , 43, 55, 56]. Indications for proceeding to transplant have included poor response to G-CSF (most common), development of G-CSFR mutation(s), inability to tolerate G-CSF injections, infection unresponsive to GCSF and anti-microbials, development of cytogenetic changes consistent with MDS, and morphologic evidence of MDS or leukemia.…”

Section: Scope Of Hctmentioning

confidence: 99%

Hematopoietic stem cell transplantation for severe congenital neutropenia

Connelly

Choi

Levine

2012

Current Opinion in Hematology

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Purpose of review Hematopoietic stem cell transplant (HCT) is the only curative option for patients with severe congenital neutropenia (SCN). Transplant success is dependent on identifying at risk patients and proceeding to transplant before the development of severe infections or malignant transformation. This review focuses on recent advancements in risk stratification of SCN patients, indications for HCT, and review of published transplant studies. Recent findings Patients with poor neutrophil response despite high doses of granulocyte colony-stimulating factor (G-CSF) are at greatest risk for malignant transformation. Other studies demonstrate elevated risk with mutations in the G-CSF receptor gene and a specific mutation in the ELANE gene. These patients are at high-risk of sepsis or leukemia development and should proceed to transplant with best available donor. As recent published studies demonstrate, HCT is highly successful in patients without leukemia and therefore may be considered in selected low-risk patients given the life-long risk of malignancy and infection. Summary The decision whether to proceed to HCT in healthy patients maintained on G-CSF is difficult. As transplant related mortality continues to decrease, the role of transplant in severe congenital neutropenia is likely to expand to more patients.

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Section: Scope Of Hctmentioning

confidence: 99%

Hematopoietic stem cell transplantation for severe congenital neutropenia

Connelly

Choi

Levine

2012

Current Opinion in Hematology

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“…9,10 In these patients, the only curative treatment is hematopoietic stem cell transplantation (HSCT). Indications for HSCT and transplant modalities are based on single case reports, small cohorts of patients, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] and national group guidelines. 28 Information derived by these heterogeneous sources report survival after HSCT at ;80% and suggest that the presence of MDS/acute myeloid leukemia at HSCT and the use of matched unrelated donors (MUDs) have a negative impact on the outcome.…”

Section: Introductionmentioning

confidence: 99%

Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation

Fioredda

Iacobelli

Biezen

et al. 2015

Blood

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Key Points• The outcome of HSCT in this large SCN cohort is acceptable.• Given the TRM, a careful selection of HSCT candidates should be undertaken.Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day 190) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken. (Blood. 2015;126(16):1885-1892 Medscape Continuing

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“…The lack of beneficial effect of G-CSF administration on neutrophil function (3) and the possible role of G-CSF administration in leukemogenesis (4) underscores the need to search for alternative therapies. Currently, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN (5).…”

Section: Introductionmentioning

confidence: 99%