To The Editor:
Sickle cell disease (SCD) is the commonest hemoglobinopathy globally.
Awaiting optimal gene manipulation strategy, hematopoietic cell
transplant (HCT) remains the only possible cure for symptomatic SCD
non-responsive to hydroxyurea.11Ribeil JA, Hacein-Bey-Abina S,
Payen E, et al. Gene therapy in a patient with sickle cell disease.
New England Journal of Medicine. 2017 Mar 2;376(9):848-55.,22Gluckman
E, Cappelli B, Bernaudin F, et al. Sickle cell disease: an
international survey of results of HLA-identical sibling hematopoietic
stem cell transplantation. Blood, The Journal of the American Society
of Hematology. 2017 Mar 16;129(11):1548-56.,33Thornburg
CD, Files BA, Luo Z, et al. Impact of hydroxyurea on clinical events
in the BABY HUG trial. Blood, The Journal of the American Society of
Hematology. 2012 Nov 22;120(22):4304-10. Human leukocyte antigen
(HLA) identical related donor transplant remains standard of care with
outcomes approaching 85-95%, whereas HLA identical unrelated donor or
haploidentical family donor (HFD-HCT) are valid clinical options with
>80% survival at experienced
centres2,44Kharya
G, Bakane A, Agarwal S, Rauthan A. Pre-transplant myeloid and immune
suppression, upfront plerixafor mobilization and post-transplant
cyclophosphamide: novel strategy for haploidentical transplant in
sickle cell disease. Bone Marrow Transplantation. 2021
Feb;56(2):492-504.. Although improving but graft failure
(primary/Secondary) and graft vs host disease (GvHD) are common
complications post HSCT followed by rare complications such as secondary
malignancies or bone marrow
hypoplasia/aplasia.55Bernaudin
F, Socie G, Kuentz M, et al. Long-term results of related
myeloablative stem-cell transplantation to cure sickle cell disease.
Blood, The Journal of the American Society of Hematology. 2007 Oct
1;110(7):2749-56.,66Dallas MH, Triplett B,
Shook DR, et al. Long-term outcome and evaluation of organ function in
pediatric patients undergoing haploidentical and matched related
hematopoietic cell transplantation for sickle cell disease. Biology of
Blood and Marrow Transplantation. 2013 May 1;19(5):820-30. We report
a child who underwent HFD-HCT for SCD and subsequently presented 1.5
years later with hypoplastic bone marrow requiring a second salvage HCT.
A seven-year-old east African boy diagnosed as SCD at the age of one
year presented to us with multiple SCD related complications since
infancy for a possible HFD-HCT in absence of HLA identical donor. He
underwent HFD-HCT with elder sister (10-years-old, 6/10 HLA match) as
donor using APOLLO protocol.4 His post-transplant
course was complicated by fungal pneumonia and BK virus induced
hemorrhagic cystitis which were managed as per unit protocol. His MMF
was tapered after 30 days post-transplant over 2 weeks, sirolimus was
tapered 9 months onwards, and he was off immunosuppression by 12 months
post HCT.
Post HCT Day + 538 he presented with complains of fever for 3 weeks
associated with oral candidiasis and poor feeding. His complete blood
counts revealed pancytopenia (Absolute neutrophil count:
300/mm3, Platelet count 8,000/mm3),
bone marrow biopsy suggestive of hypo-cellular marrow with significantly
decreased cellularity and 100% donor chimerism. He required multiple
transfusions and extended use of antibiotics and antifungals for
management of bacterial sepsis and fungal pneumonia. In view of his
symptomatology, parents were counselled regarding the need for second
salvage transplant. After taking informed consent he underwent a
2nd salvage HCT using same donor. The transplant
details during 1st and 2nd HCT are
highlighted in Table 1. He tolerated conditioning well and had
neutrophil and platelet engraftment on day 14 and 15 respectively. His
post-transplant course was complicated by klebsiella sepsis, cytokine
release syndrome (CRS) Gr II, engraftment fever (EF) and drug induced
hemorrhagic cystitis. All the complications were managed as per unit
protocols. As of 25/01/22, he is 140 days post HCT, doing well
clinically with no evidence of acute or chronic GvHD, 100% donor
chimerism and good immune reconstitution (absolute CD4 and CD19, 443 and
831 cells/mm3 respectively at day 100).
The definitive incidence and treatment of aplasia post HCT for SCD is
still not clear. It has been rarely documented and treated with
2nd HCT.5 The etiology of aplasia
and donor chimerism have not been documented clearly in previous
reports. Our patient had 100% donor chimerism at the time of
presentation with marrow hypoplasia. There is no clear-cut understanding
and guidelines for choice of conditioning chemotherapy in such scenario.
We decided to go with reduced toxicity conditioning with low dose of
serotherapy.
We report successful 2nd salvage HCT in a child with
acquired hypoplastic anemia of donor marrow. Our experience suggests
that 2nd HCT using same donor and reduced toxicity
conditioning is a viable clinical option in a rare clinical setting
where previous literature is sparse.