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|Year : 2021 | Volume
| Issue : 4 | Page : 235-237
Recurrent aplastic anemia with donor-type aplasia: A rare occurrence in the Indian subcontinent
A Majumder, S Misra, V Kumar
Department of Pathology, ABVIMS and Dr. RML Hospital, New Delhi, India
|Date of Submission||23-Aug-2020|
|Date of Decision||06-Dec-2020|
|Date of Acceptance||30-Dec-2020|
|Date of Web Publication||01-Jun-2021|
Department of Pathology, ABVIMS and Dr. RML Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Donor-type aplasia (DTA) is a condition where an individual continues to be aplastic even after a successful engraftment of a hematopoeitic stem cell transplant with a majority of donor type cells in the bone marrow. This entity has been seen with varying frequency around the world, especially in Southeast Asia. However, its incidence in the Indian subcontinent remains fairly low. Here is a case of a 17-year-old child with DTA who had a 89% population of donor cells after a successful transplant and presented with recurrent severe aplastic anemia later. The patient eventually succumbed to his condition before a second transplant could be performed. The awareness about the seriousness of this relatively rare condition, therefore, needs to be emphasized.
Keywords: Bone marrow transplant, chimerism, donor-type aplasia, hematology, hematopoeitic stem cells
|How to cite this article:|
Majumder A, Misra S, Kumar V. Recurrent aplastic anemia with donor-type aplasia: A rare occurrence in the Indian subcontinent. J Postgrad Med 2021;67:235-7
|How to cite this URL:|
Majumder A, Misra S, Kumar V. Recurrent aplastic anemia with donor-type aplasia: A rare occurrence in the Indian subcontinent. J Postgrad Med [serial online] 2021 [cited 2022 Sep 30];67:235-7. Available from: https://www.jpgmonline.com/text.asp?2021/67/4/235/318035
| :: Introduction|| |
Severe Aplastic Anemia as defined by the modified Camitta criteria includes a marrow cellularity <25% (or 25–50% with <30% residual haematopoietic cells), plus at least 2 of: (i) neutrophils <500/μL, (ii) platelets <20.000/μL, (iii) reticulocyte count <20.000/μL. The widely accepted treatment of idiopathic severe aplastic anemia (SAA) in childhood is hematopoeitic stem cell transplant (HSCT) with a human leucocyte antigen (HLA) matched sibling donor (MSD) or a matched unrelated donor (MUD) along with concomitant immunosuppressive therapy (IST). The natural expectation would be to attain a full donor chimerism of 100% or a high donor majority in a mixed chimeric picture to ensure complete engraftment. However, recent studies have shown that a mixed chimerism is favorable as it reduces the chance of acute graft vs host disease (GvHD). In the recent years, there have been sporadic reported cases of a late graft failure after a successful transplant and engraftment of >6 months, usually after the stoppage of IST. Interestingly, some of these cases have shown to have a majority of donor cells in the marrow during this recurrence. This has been termed as donor-type aplasia (DTA). This case highlights the importance of this relatively rare entity in this geographic area.
| :: Case Report|| |
Here we present the case of a 17-year-old male who was diagnosed as aplastic anemia in December 2018 (absolute neutrophil count 400/cu.mm, platelets 10000/cu.mm) and underwent bone marrow transplantation with a MSD on April 2019. The conditioning regimen offered was fludarabine (Flu) with reduced dose cyclophosphamide and anti-thymocyte globulin (ATG). The procedure was followed by successful engraftment and returning of blood counts to normal levels (Hemoglobin [Hb]: 12.1 gm/dl, total leucocyte count [TLC]: 5900/cu.mm, platelet count [PC]: 1.6 lakhs/cu.mm). Post-transplant IST was started in the form of cyclosporine (CsA) without ATG. The patient continued taking CsA without any obvious adverse effects for a year from April 2019 to March 2020. Repeat CBCs showed a stabilization of blood counts. Serial tests for chimerism done by short tandem repeats-polymerase chain reaction (STR-PCR) within the period May 2019 to February 2020 showed an average of 93% donor cells in the marrow (peak of 96%). After almost two and half months of stoppage of CsA, the patient's condition deteriorated in late May 2020. There were two episodes of bleeding from the nose and mouth and progressive pallor was noted. CBC showed the following parameters: Hb-5.6 gm/dl, TLC -3200/cu.mm, PC -30000/cu.mm. There was no history of trauma/viral infection. Bone marrow was sent for examination. The aspirate was hemodilute with few cellular trails showing trilineage hematopoiesis. The biopsy was hypoplastic with a cellularity of 20-25% [Figure 1]a. There was an apparent mild increase in lymphoid cells. Repeat bone marrow chimerism studies showed 89% donor cells [Figure 1]b. Packed red cells and platelet infusions were given for symptomatic relief. As the clinical condition continued to deteriorate rapidly, a second HSCT from the same sibling was planned with a clinical suspicion of DTA. No additional IST/medication was given. However, the patient succumbed to his critical illness before the second transplant could be attempted in June 2020.
|Figure 1: (a) Bone marrow biopsy showing pauci-cellular marrow spaces (black arrow) (H and E ×100). (b) Graph showing variation of donor cell percentage in sequential marrow-chimerism studies over a period of one-year post-transplant. (SD- standard deviation; CV- coefficient of variation)|
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| :: Discussion|| |
DTA has been documented in cases occurring 8 months to 10 years post-transplant. Its incidence varies from 5% to 26% in various studies., A number of mechanisms have been theorized for the same. It is speculated that the destruction of the donor cells is more protracted than what was thought initially and that the “malignant” recipient clone eventually takes over the marrow again. As in some cases the onset of DTA was seen along with an underlying viral infection, it is thought that a secondary infectious trigger which leads to the prolonged activation of pathogen specific T cells of recipient origin could also be the mechanism for aplasia. It is also of importance to note that although SAA is usually idiopathic, some cases of recurrence has been noted among MSDs. Thus there is a possibility of a genetic role in such cases which warrants further investigations by whole genome sequencing. Patients after HSCT are also less responsive to indigenous erythropoietin, thereby worsening the state of anemia. Other factors like low infused cell number, no IST prior to HSCT, preceding transfusion >40 times and inclusion of fludarabine therapy along with CsA were associated with the development of donor-type aplasia.,
The probable reasons for development of DTA in this particular case are varied. The patient underwent a high number of pre transplant transfusion (>40). Although viral markers were negative, subclinical viral infections could have caused a “second hit”, thereby leading to protracted recipient T-cell activation. Clonal evolution of the “aplastic clone” also remains a possible cause, warranting the need for whole genome studies in such patients. In addition to these, the exclusion of ATG from post-transplant regimen and a possible early withdrawal of CsA could be added causative factors here.
A second HSCT from the primary donor remains the treatment of choice in patients of DTA. In some cases pre-transplant treatment by CD34 infusions, steroids, CsA, ATG, donor lymphocyte infusion (DLI), plasmapheresis, rituximab, sirolimus, or eltrmpobag may be used. Out of these, only eltrombopag has been reported to cause sustained improved cell counts. Occasional cases may even require a third transplant. However, caution should be exercised because in spite of protective treatments, HSCT itself can cause a plethora of complications including GvHD, organ damage, infections, failure of stem cell transplant (primary and secondary) and rarely, hemolytic uremic syndrome and myelodysplasia.
DTA is a relatively rare entity. Owing to the severity and possible fatal outcome, this condition should be borne in mind by clinicians and pathologists alike.
Declaration of patient consent
The authors certify that appropriate patient consent was obtained.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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