Introduction:
Introduction
Haematological stem cell transplant is the gold standard of therapy for numerous malignant and non-malignant haematological disorders. Chronic kidney disease incidence post HSCT is almost up to the range of 15-20 %.
The etilogies include chronic radiation therapy, viral infections, chronic calcineurin inhibitor therapy and the most common histological phenotype is a thrombotic microangiopathy like picture.
Chronic GVHD can also present with TMA like picture indicating an endothelial injury as possible manifestation of the disease.
This case talks about a rare presentation of TMA in a case of AML post hematopoietic stem cell transplant.
Methods:
This is a case of a 40-year-old male who back in April 2022 with normal renal functions, had nil-comorbidities presented with fever, generalised fatigue and oral ulcers. On evaluation, he was found to have low haemoglobin (3 gm/dl), elevated total counts (1.16 lakhs) and thrombocytopenia. (44,000)
The peripheral smear showed a normocytic normochromic anaemia and blast cells with Auer roads with thrombocytopenia. Bone marrow biopsy confirmed the findings of acute leukaemia with 85% blast cells. Genetic analysis was done which was positive for CEBPA bilalleic mutation, NRAS, IK2F mutation. Flow cytometry showed positivity for CD 123, CD 34, CD 7, CD 56, CD 200, CD 117 and cytoplasmic MPO.
Subsequently, he underwent induction therapy with 3+7 regimen (cytarabine and daunorubucin) and consolidation with high dose cytarabine (HiDAC), he achieved remission of his disease with no major chemotherapy related complications and bone marrow showed resolution of disease by august 2022.
In the month of January,2023 patient complained of headache and leg pain with complaints of bowel incontinence. Imaging done at the point of time was suggestive of skeletal metastasis and histopathology showed features of non-Langerhans cells histiocytosis for which he received radiation therapy.
For the headache, neuroimaging was suggestive of meningeal metastasis.
At this point, his blood and peripheral smear were normal.
Cerebrospinal fluid analysis was done which was suggestive of 2000 cells with 90% atypical cells and flow cytology and cytometry was suggestive of acute myeloid leukemia with meningeal metastasis.
He completed salvage chemotherapy with high dose cytarabine and venetoclax and underwent peripheral stem cell transplant in the month of July 2023 with his daughter (11 year old female) which was an ABO incompatible transplant with a 6/10 HLA match.
In the immediate post transplant period, he developed sepsis which was adequately managed with IV antibiotics. For graft versus host disease prophylaxis, he was given cyclophosphamide, tacrolimus and Mycophenolate mofetil and his tacrolimus and MMF was continued post discharge.
Throughout this period, he had normal renal functions with a baseline creatinine of 0.9mg/dl till November of 2023. His tacrolimus and MMF was tapered by this period of time.
Post this period, he had slowly peaking creatinine with good blood pressure control, no frothy urine or hematuria.
His urine protein creatinine ratio was 0.7 and renal artery doppler was unremarkable.
The acute myeloid leukaemia was also in remission.
Results:
In view of progressive renal dysfunction and sub nephrotic range proteinuria, he underwent renal biopsy which showed-
Basement membrane duplication with subendothelial space widening and transmigration of RBC in the sub endothelium and capillary microaneurysms formation secondary to mesangiolysis. There was marked basement membrane remodelling. The tubules showed mild IFTA (20 %) and vessels showed evidence of mild fibrointimial thickening.
Immunofluorescence was negative for Immunoglobulins, complements and no light chain restriction and these changes were suggestive of chronic thrombotic microangiopathy. In the setting of post hematopoietic stem cell transplant, chronic glomerular TMA was attributed to chronic graft versus disease and patient was started on prednisolone 30mg/day and is currently doing well on follow up.
Conclusions:
CONCLUSION
Our case presented without hypertension, nephrotic syndrome, or extrarenal GVHD manifestations.. In conclusion, we herein reported a case of HSCT nephropathy associated with chronic GVHD without obvious extrarenal involvement. The slowly rising creatinine was in sync with with the withdrawal of immunosuppression indicating a chronic GVHD as the probable cause of his chronic TMA. Although typical GVHD-related nephropathy presents with clinical manifestations, it may also occur without any obvious extrarenal involvement.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.