EHA Library - The official digital education library of European Hematology Association (EHA)

MANAGEMENT OF ELANE-NEUTROPENIA: LIFETIME G-CSF VS HAEMATOPOIETIC STEM CELL TRANSPLANTATION LEARNING LESSON FROM THE EXPERIENCE
Author(s): ,
Francesca Fioredda
Affiliations:
Haematology Unit,IRCCS Giannina Gaslini,Genova,Italy
,
Filomena Pierri
Affiliations:
Haematology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italy
,
Marina Lanciotti
Affiliations:
Haematology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italy
,
Sabrina Zanardi
Affiliations:
Biostatistic and Epidemiology Unit,IRCCS Istituto Giannina Gaslini,Genova,Italy
,
Bobby Gaspar
Affiliations:
Infection, Immunity, Inflammation, Molecular and Cellular Immunology Section,University College London,London,United Kingdom
,
Phil Ancliff
Affiliations:
Department of Haematology,Great Ormond Street Hospital Children's Charity,London,United Kingdom
,
Marc Bierings
Affiliations:
Pediatric Blood and Marrow Transplantation Program,Wilhelmina Children's Hospital, University Medical Center Utrecht,Utrecht,Netherlands
,
Gulyuz Ozturk
Affiliations:
Acıbadem University Atakent Hospital,Instanbul,Turkey
,
Owen Smith
Affiliations:
Department of Pediatric Hematology,Our Lady’s Children’s Hospital,Dublin,Ireland
,
Paul Veys
Affiliations:
Bone Marrow Transplant Unit,Great Ormond Street Hospital ,London,United Kingdom
,
Per Ljungman
Affiliations:
Haematology Unit,Karolinska Institutet,Stockholm,Sweden
,
Régis Peffault de la Tour
Affiliations:
Service d'hématologie greffe,Hôpital Saint-Louis ,Paris,France
,
Reuven Or
Affiliations:
Department of Bone Marrow Transplantation,Hadassah University Hospital,Jerusalem,Israel
,
Robert Wynn
Affiliations:
Department of Paediatric Haematology Bone Marrow Unit,Royal Manchester Children's Hospital,Manchester,United Kingdom
,
Krzysztof Kalwak
Affiliations:
Pediatric Hematology/Oncology and BMT,Medical University of Wroclaw,Wroclaw,Poland
,
Giovanna Russo
Affiliations:
Pediatric Hematology/Oncology Unit,Policlinico Vittorio-Emanuele, Università di Catania,Catania,Italy
,
Fabio Tucci
Affiliations:
Pediatric Hematology/Oncology Unit,Meyer,Firenze,Italy
,
Christine Knoll
Affiliations:
Hematology/Oncology,Phoenix Children's Hospital,Phoenix,United States
,
Baldo Martire
Affiliations:
OncoEmatologia ed Immunologia Pediatrica,Policlinico Bari,Bari,Italy
,
Claudio Favre
Affiliations:
Oncoematologia Pediatrica,Meyer Hospital,Firenze,Italy
,
Christine Bellanné-Chantelot
Affiliations:
Département de Génétique, ,AP-HP Hôpital Pitié-Salpêtrière, UPMC Univ Pitiè-Salpetriere Hospital,Paris,France
,
Blandine Beaupain
Affiliations:
Service d'Hémato Oncologie Pédiatrique, Registre des neutropénies congénitales,AP-HP Hopital Trousseau,Paris,France
,
Jean Donadieu
Affiliations:
Service d'Hémato Oncologie Pédiatrique, Registre des neutropénies congénitales,AP-HP Hopital Trousseau,Paris,France
Carlo Dufour
Affiliations:
Haematology Unit,IRCCS Giannina Gaslini,Genova,Italy
(Abstract release date: 05/17/18) EHA Library. Fioredda F. 06/17/18; 214587; S1582
Ms. Francesca Fioredda
Ms. Francesca Fioredda
Contributions
Abstract

Abstract: S1582

Type: Oral Presentation

Presentation during EHA23: On Sunday, June 17, 2018 from 08:30 - 08:45

Location: Room A8

Background

 Severe Congenital Neutropenia (SCN) due to ELANE mutations  is usually managed with Granulocyte–Colony Stimulating Factor (G-CSF) but may also be amenable for treatment with  Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). According to the experts, HSCT is indicated  in patients transformed into MDS/AL  or who are refractory/poor responding  to G-CSF (> 20 mcg/kg/day). HSCT looks also appropriate for those subjects treated with G-CSF at doses between 10-20 mcg/kg/d, while the indications for those subjects managed with doses up to 10 mcg/kg are less clear.

Aims
To retrospectively compare  the long term outcome of SCN-ELANE  patients who underwent HCST vs those who did not, stratified according to G-CSF dose .

Methods
 Data have been extracted from the Severe Chronic Neutropenia French registry (SCNFR), the Italian Neutropenia Registry (INR), from the database  of the  Severe Aplastic Anemia Working Group of the European Society for Blood and Marrow Transplantation (EBMT) and from Stem Cell Transplant for Immunodeficiencies in Europe (SCETIDE) in the years 1990-2017. The received dose of G-CSF was estimated by calculating the amount of drug that patients received for more than 75% of the treatment time (when daily dose was not available for the whole treatment period) or by calculating the mean dose (total amount/days of treatment) whenever daily dose was available for the full period. The cohort has been arbitrarly stratified in  two subgroups according to the dose of   G-CSF received: ≤10 mcg/kg/d, and >10 mcg/kg/d.

Results

162 SCN ELANE patients were considered eligible for the study, 141 were treated with G-CSF and 52 received  HSCT. Transplant indication was as per Center policy. Characteristics of the population are shown in Table 1. The 15 y-OS of the whole group was 91% (95% IC; 84-95). HSCT patients had worse survival vs those treated with G-CSF: 79% (95% IC; 52-92) vs 94% (95% IC 87-97) respectively  (p=0.031).   The 15y-OS of patients receiving G-CSF  >11mcg/kg/d  was 85% (95% IC; 51-96)  vs 74% (95% IC 33-92) of  HSCT patients  (p 0.325). Transplanted patients receiving ≤ 10mcg/kg/d of G-CSF had significantly lower 15-yr OS  if compared with the G-CSF treated subjects (74% -95% IC 24-94 vs 98% -95% IC 91-99-) (p=0.015). In the subgroup treated with  G-CSF ≤ 10mcg/kg/d who underwent HSCT,  1 patients had AL, 1 had  unmanageable infections and 5 had available an identical siblings. Comparison of OS in the two groups by additional “risk factors” other than  CSF dose is ongoing.

Conclusion

This is the largest comparative analysis  between  HSCT and  life-time G-CSF conducted in  ELANE-SCN cohort . The OS of  the whole cohort 91 % after 15 y of follow up. On the whole the HSCT group  shows a significantly worse survival vs G-CSF treated one probably because a negative selection of the transplanted patients . However the OS of the group who received G-CSF ≤10mcg/kg/d and underwent HSCT was significantly inferior than that managed with G-CSF alone  . This suggests that indication to transplant for patients receiving G-CSF dose ≤10mcg/kg/d needs to be carefully balanced. Definitive conclusion might be drawn at the completion of analysis  including other factors that may affect the outcome like  molecular characteristics, clonal evolution markers and infection load.  

Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical

Keyword(s): Granulocyte colony-stimulating factor (G-CSF), Severe congenital neutropenia, Stem cell transplant

Abstract: S1582

Type: Oral Presentation

Presentation during EHA23: On Sunday, June 17, 2018 from 08:30 - 08:45

Location: Room A8

Background

 Severe Congenital Neutropenia (SCN) due to ELANE mutations  is usually managed with Granulocyte–Colony Stimulating Factor (G-CSF) but may also be amenable for treatment with  Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). According to the experts, HSCT is indicated  in patients transformed into MDS/AL  or who are refractory/poor responding  to G-CSF (> 20 mcg/kg/day). HSCT looks also appropriate for those subjects treated with G-CSF at doses between 10-20 mcg/kg/d, while the indications for those subjects managed with doses up to 10 mcg/kg are less clear.

Aims
To retrospectively compare  the long term outcome of SCN-ELANE  patients who underwent HCST vs those who did not, stratified according to G-CSF dose .

Methods
 Data have been extracted from the Severe Chronic Neutropenia French registry (SCNFR), the Italian Neutropenia Registry (INR), from the database  of the  Severe Aplastic Anemia Working Group of the European Society for Blood and Marrow Transplantation (EBMT) and from Stem Cell Transplant for Immunodeficiencies in Europe (SCETIDE) in the years 1990-2017. The received dose of G-CSF was estimated by calculating the amount of drug that patients received for more than 75% of the treatment time (when daily dose was not available for the whole treatment period) or by calculating the mean dose (total amount/days of treatment) whenever daily dose was available for the full period. The cohort has been arbitrarly stratified in  two subgroups according to the dose of   G-CSF received: ≤10 mcg/kg/d, and >10 mcg/kg/d.

Results

162 SCN ELANE patients were considered eligible for the study, 141 were treated with G-CSF and 52 received  HSCT. Transplant indication was as per Center policy. Characteristics of the population are shown in Table 1. The 15 y-OS of the whole group was 91% (95% IC; 84-95). HSCT patients had worse survival vs those treated with G-CSF: 79% (95% IC; 52-92) vs 94% (95% IC 87-97) respectively  (p=0.031).   The 15y-OS of patients receiving G-CSF  >11mcg/kg/d  was 85% (95% IC; 51-96)  vs 74% (95% IC 33-92) of  HSCT patients  (p 0.325). Transplanted patients receiving ≤ 10mcg/kg/d of G-CSF had significantly lower 15-yr OS  if compared with the G-CSF treated subjects (74% -95% IC 24-94 vs 98% -95% IC 91-99-) (p=0.015). In the subgroup treated with  G-CSF ≤ 10mcg/kg/d who underwent HSCT,  1 patients had AL, 1 had  unmanageable infections and 5 had available an identical siblings. Comparison of OS in the two groups by additional “risk factors” other than  CSF dose is ongoing.

Conclusion

This is the largest comparative analysis  between  HSCT and  life-time G-CSF conducted in  ELANE-SCN cohort . The OS of  the whole cohort 91 % after 15 y of follow up. On the whole the HSCT group  shows a significantly worse survival vs G-CSF treated one probably because a negative selection of the transplanted patients . However the OS of the group who received G-CSF ≤10mcg/kg/d and underwent HSCT was significantly inferior than that managed with G-CSF alone  . This suggests that indication to transplant for patients receiving G-CSF dose ≤10mcg/kg/d needs to be carefully balanced. Definitive conclusion might be drawn at the completion of analysis  including other factors that may affect the outcome like  molecular characteristics, clonal evolution markers and infection load.  

Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical

Keyword(s): Granulocyte colony-stimulating factor (G-CSF), Severe congenital neutropenia, Stem cell transplant

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