T Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation for Patients with Familial Hemophagocytic Lymphohistiocytosis Who Do Not Have Matched Family Donors: Experience in Oman

Abstract

Familial hemophagocytic lymphohistiocytosis (FHLH) is a potentially fatal disorder of immune regulation. Management includes chemotherapy followed by hematopoietic stem cell transplantation (HSCT). T cell depleted (TCD)-haploidentical HSCT could be an option for those patients who do not have HLA matching family donor. The objective of this study was to report on the outcome of TCD-haploidentical HSCT in patients with FHLH who underwent transplantation at Sultan Qaboos University Hospital (SQUH). This is a retrospective report on 12 patients with FHLH who received TCD-haploidentical HSCT at SQUH between August 2010 and December 2018. Epidemiologic characteristics and details on the transplantation procedures and complications were collected from patients' electronic records. Twelve patients with FHLH received TCD-haploidentical HSCT after a myeloablative conditioning regimen composed of treosulfan/thiotepa/fludarabine/anti-thymocyte globulin and rituximab. The mean age at transplantation was 11.67 § 8 months. All patients had Perforin gene mutations, except 1 patient who had an UNC-13D mutation. Most patients received TCRab + /CD19 + depleted grafts for faster immune reconstitution. Seven patients (58.3%) have been cured with a mean follow-up duration of 3.44 years. Four patients died of multiorgan failure secondary to gram-negative sepsis. One patient had primary graft failure, and 2 patients had mild graft-versus-host disease. Two patients had Pneumocystis carinii pneumonia, 2 had adenoviremia, and 9 patients had cytomegalovirus (CMV) viremia. Among patients with CMV viremia, 2 had evidence of disease (retinitis, enteritis). All patients with CMV viremia were treated successfully with foscarnet pre-engraftment and ganciclovir postengraftment, respectively. TCD-haploidentical HSCT could be a viable option for patients with FHLH who do not have HLA matching family donors. Infectious complications are the leading cause of death in that setting. CMV viremia was the most frequently encountered infectious complication.

Precautions are Needed for COVID-19 Patients with Coinfection of Common Respiratory Pathogens

“…conducted in Wuhan showing that there was no coinfection of respiratory pathogens in COVID-19 cases. 3,9 According to our data, the majority of COVID- 19 Here we also compared the geographical and climatic characteristics of Qingdao and Wuhan. Wuhan is located in the centre of southern China and has a subtropical climate; 16,17 while Qingdao is situated in the coastal area of northern China in the temperate zone, which has a relatively lower humidity than Wuhan.…”

“…18 Despite the difference in natural characteristics between the two cities, common respiratory pathogens circulate in Wuhan and Qingdao (including IFV-A, IFV-B, RSV, and ADV) have shown to be generally similar during the peak season of respiratory diseases in wintertime (from January to February). [19][20][21][22] The incidence of coinfection in COVID-19 patients in Wuhan was rather low. Whereas in places with relatively low temperature like northern Qingdao, it is more common to find combined SARS-CoV-2 infection with other seasonal respiratory pathogens.…”

“…We recruited patients with laboratory-confirmed COVID- 19 This study was approved by the Ethics Commission of each participating hospital (QFFLL-KY-2020-11) and written informed consent was obtained from involved patients prior to enrolment.…”

“…On December 31, 2019, a total of 27 cases were reported; meanwhile, a rapid response team led by the Chinese Centre for Disease Control and Prevention (China CDC) was formed to conduct detailed epidemiologic and aetiologic investigations in Wuhan. [1][2][3] After ruling out common respiratory pathogens such as influenza, avian influenza, respiratory syncytial virus (RSV), adenovirus (ADV), respiratory severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), etc., a novel coronavirus was confirmed as the aetiological agent on January 7, 2020 and related disease was termed as Coronavirus Disease 2019 (COVID- 19) by the World Health Organisation (WHO). 4 Subsequent full-length genome sequencing analysis indicated that the newly discovered virus, now known as severe acute respiratory coronavirus 2 (SARS-CoV-2), belongs to a distinct beta-coronavirus genus of probable bat origin.…”

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

“…Through TCR a+b+/CD19+ cell-depleted haploSCT, it is feasible to transfer to the transplant recipient both donor hematopoietic stem cells (HSCs) and hematopoietic progenitors as well as NK and gd T cells, which could protect against leukemia and life-threatening infections, including posttransplant lymphoproliferative disease (PTLD). A total of 7.27-75% of patients undergoing TCR a+b+/CD19+ cell depleted HSCT experienced CMV reactivation (42)(43)(44)(45)(46). Most patients experienced CMV viremia during the first month after haploSCT (days +1 to +24) (45).…”