Contributions
Abstract: PB1789
Type: Publication Only
Session title: Stem cell transplantation - Clinical
Background
Chronic Granulomatous Disease (CGD) is an inherited congenital disorder characterized by severe recurrent infections and inflammatory complications due to defects in phagocyte oxidative function. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently the only established curative treatment, but it remains a challenge to decide which patients (and when) should proceed to transplant. Historically, alloHSCT in these patients was associated with greater risk of graft failure, low donor chimerism, and mortality due to previous organ dysfunction, compared to other primary immunodeficiency disorders.
Aims
To describe baseline characteristics and outcomes of patients with CGD treated with alloHSCT in our Institution.
Methods
Retrospective descriptive analysis of patients with CGD who received an alloHSCT in our Institution between 2009 and 2018.
Results
In the 10-year period considered in this study, 5 patients (4 boys and one girl) were referred to our Institution and received an alloHSCT for CGD. All had severe and recurrent infections and most (n=4) had also inflammatory conditions (most frequently granulomatous colitis) leading to diagnosis, which was confirmed at a median age of 8 months (5 months-13 years). Most (n=3) had an X-linked genotype (CYBB gene mutation) and 2 had an autosomal recessive genotype (CYBA and NCF1 gene mutations).
Median age at transplant was 7 years (1-15 years). Two patients received a matched sibling transplant from peripheral blood progenitors, and the remainder received a matched unrelated donor transplant from bone marrow (n=2) and cord blood (n=1) progenitors. There was no documented active infection at time of transplant. Most patients (n=4) received a myeloablative conditioning regimen with busulfan+cyclophosphamide, and additional anti-thymocyte globulin in 2 cases. Median time of in-patient care during peri-transplant period was 29 days (25-74 days). All patients had febrile neutropenia during the pre-engraftment period controlled with large spectrum antimicrobials.
Median time to engraftment was 17 days (13-55 days). Acute graft-versus-host disease (GVHD) was documented in 2 patients (grades 1 and 2). Full donor chimerism was attained in 3 patients at a median time of 41 days (32-54 days). Mixed and falling donor chimerism was observed in the other 2 patients, who had received bone marrow reduced-intensity conditioning and cord blood HSCT. They had secondary graft failure and proceeded to a second alloHSCT, at 8 and 17 months after the first transplant (from different matched unrelated donors, graft source was peripheral blood in both cases).
With a median follow-up time from first alloHSCT of approximately 8 years (1.7-10.7 years), 4 patients are alive and without manifestations of CGD. Three patients have developed chronic GVHD, mostly cutaneous and mild. CMV reactivation was documented in 4 patients and one had post-transplant EBV-related lymphoproliferative disease successfully treated with rituximab. One patient died at 3 months after second alloHSCT from associated complications.
Conclusion
CGD patients remain a challenge in the alloHSCT setting due to susceptibility to infectious and inflammatory complications. However, improvement of conditioning regimens and peri-transplant supportive care have contributed to better outcomes in this population.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Chronic granulomatous disease
Abstract: PB1789
Type: Publication Only
Session title: Stem cell transplantation - Clinical
Background
Chronic Granulomatous Disease (CGD) is an inherited congenital disorder characterized by severe recurrent infections and inflammatory complications due to defects in phagocyte oxidative function. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently the only established curative treatment, but it remains a challenge to decide which patients (and when) should proceed to transplant. Historically, alloHSCT in these patients was associated with greater risk of graft failure, low donor chimerism, and mortality due to previous organ dysfunction, compared to other primary immunodeficiency disorders.
Aims
To describe baseline characteristics and outcomes of patients with CGD treated with alloHSCT in our Institution.
Methods
Retrospective descriptive analysis of patients with CGD who received an alloHSCT in our Institution between 2009 and 2018.
Results
In the 10-year period considered in this study, 5 patients (4 boys and one girl) were referred to our Institution and received an alloHSCT for CGD. All had severe and recurrent infections and most (n=4) had also inflammatory conditions (most frequently granulomatous colitis) leading to diagnosis, which was confirmed at a median age of 8 months (5 months-13 years). Most (n=3) had an X-linked genotype (CYBB gene mutation) and 2 had an autosomal recessive genotype (CYBA and NCF1 gene mutations).
Median age at transplant was 7 years (1-15 years). Two patients received a matched sibling transplant from peripheral blood progenitors, and the remainder received a matched unrelated donor transplant from bone marrow (n=2) and cord blood (n=1) progenitors. There was no documented active infection at time of transplant. Most patients (n=4) received a myeloablative conditioning regimen with busulfan+cyclophosphamide, and additional anti-thymocyte globulin in 2 cases. Median time of in-patient care during peri-transplant period was 29 days (25-74 days). All patients had febrile neutropenia during the pre-engraftment period controlled with large spectrum antimicrobials.
Median time to engraftment was 17 days (13-55 days). Acute graft-versus-host disease (GVHD) was documented in 2 patients (grades 1 and 2). Full donor chimerism was attained in 3 patients at a median time of 41 days (32-54 days). Mixed and falling donor chimerism was observed in the other 2 patients, who had received bone marrow reduced-intensity conditioning and cord blood HSCT. They had secondary graft failure and proceeded to a second alloHSCT, at 8 and 17 months after the first transplant (from different matched unrelated donors, graft source was peripheral blood in both cases).
With a median follow-up time from first alloHSCT of approximately 8 years (1.7-10.7 years), 4 patients are alive and without manifestations of CGD. Three patients have developed chronic GVHD, mostly cutaneous and mild. CMV reactivation was documented in 4 patients and one had post-transplant EBV-related lymphoproliferative disease successfully treated with rituximab. One patient died at 3 months after second alloHSCT from associated complications.
Conclusion
CGD patients remain a challenge in the alloHSCT setting due to susceptibility to infectious and inflammatory complications. However, improvement of conditioning regimens and peri-transplant supportive care have contributed to better outcomes in this population.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Chronic granulomatous disease