Renal transplantation in marrow dysfunction: A case series

T. Rajarajan

Consultant Nephrologist, Kauvery Hospital, Tennur, Trichy

Background

We have done renal transplants in 3 patients with aplastic anaemia. As far as our search is concerned, we found 1 case report of such a scenario in the world, only one case report from Manipal hospital Bengaluru published in KI under letters to editor column.

Introduction

Bone marrow failure (BMF)

Decreased production of one or more major hematopoietic lineages leads to diminished or absent hematopoietic precursors in the bone marrow and attendant cytopenias.

Neal S. Young, M.D. N Engl J med 379; 17 nejm.org. 2018

Normal BM

Aplastic BM

Dysplasia in MDS

Prognosis of aplastic anaemia depends

1. Severity of disease based on absolute neutrophil count

Non severe – >500
Severe 200-500
More severe – <200

2. Age at diagnosis and start of treatment.

Older the age and delay in treatment

3. Cause of aplastic anemia.

Cytogenetic abnormalities

Neal S. Young, M.D. N Engl J med 379; 17 nejm.org. 2018

Prognosis

With current BMT regimen, most patients with severe aplastic anemia have a 60-70% long-term survival rate

Patients with severe aplastic anemia who receive antithymocytic globulin (ATG) or antilymphocyte globulin (ALG) but do not receive BMT have a 41%r response rate and a 1-year survival rate of 55.4%. Adding androgens increases response rates to 70%, with a 1-year survival rate of 76%.

Cyclosporine therapy at 200-400 mg/dl (Maintain serum trough levels at 100-250 nb/mL) has a reported 85%hematologic remission rate.

Survival of dialysis vs transplant

Nephrol Dial Transplant, Volume 14, Issue 12, December 1999, Pages 2849–2854

Case Presentation

Case 1

A 37-year-old male patient came with the following complaints. ESRD (End-Stage Renal Disease) on HD NKD (No Kidney Disease.). Underwent live related renal transplant – Aug 2016, elsewhere mother donor. On Steroid, free protocol then noted a Progressive graft dysfunction. Incisional hernia in 2020 for that Mesh hernioplasty done followed by HD started 2021 December.

On routine evaluation on 23-11-2021

Hb – 5.8 g/dl; TLC – 2900; DC: N – 65.3%; L – 24.2%; M7.4 %; E – 2.4%
Platelet – 143000
Vitamin b₁₂ and folate levels were normal.

Bone marrow aspiration 23-11-21

Marrow is hypocellular.
Cellularity in hypocellular area -15%.Megakaryocytes- nil erythroid and myeloid series –unremarkable.No increase inreticulin fibres.NO granuloma,immature precursors.

Chromosome analysis: 46 XY.

Diagnosis

Non-severe Aplastic anaemia

Prognosis: Good

No cytogenetic abnormalities
Non severe aplastic anaemia
No dysplasia or immature precursors

Treatment given

Drug	Dose	Frequency
Danazol	100 mg	1-0-1
Eltrombopag	100 mg	1-0-0

Attained clinical response as evidenced by;

Discussion

Points in favour of renal transplant

Non-severe aplastic anemia with good long-term prognosis
Consistent improvement in Blood counts.
Non-requirement of transfusion, infections or bleeding diathesis
Proceeded with renal transplant as patient and family members are keen in renal transplant, as he was not doing well with dialysis.

Donor spouse – 29/f B+

HLA – Haplomatch; DSA – Negative; PRA – Negative; CM – Negative.

Pre Op counts

Hb – 9.6; TLC – 4400; N – 60 %; Platelets – 2.63 lakhs

Renal transplant on 15-8-2022

Induction: ATLG (Anti-T-Lymphocyte Globulin)

Immunosuppression: Tacrolimus (TAC)/Mycophenolate mofeti (MMF)/Steroids

L lap donor nephrectomy
Single renal vessels
Left renal bed

Therapeutic dilemmas

Induction agent

ATLG vs Basiliximab

ATG is set to be an immunosuppressive agent in treating aplastic anemia.
ATLG quite similar to ATG given in view of cost constraints

Maintenance immunosuppression

Tacrolimus/MMF/steroids vs Tacrolimus/Everolimus/steroids
In view of stable counts, High-risk transplant decided to go with Tac/mmf/steroids. Outcome was good.

Discharge

Danzol was stopped and Eltrombopag continued for 1-month post-transplant.

Hb:9.6; TLC: 6700; Platelet – 2.63
creatinine: 0.96

Last, follow up

Hb :13.5 TLC 7200 Plat : 1.9 lakhs
creatinine – 0.86

Case 2

A 42-year-old male patient came with the following complaints, CKD diagnosed 2020 and HD was inducted in Jan 2020, elsewhere. Started on transplant work up elsewhere.

Lab: Hb – 8.3; TLC – 2000; DLC – 50%; Platelet – 1.74.

Cytogenetics: No abnormality detected

Started on Danazol/Eltrombopag/Erythropoietin.

Date	Hb	TLC	N %	Platelets
10-10-21	9.6	3200	62	1.74
21-12-21	9.8	2800	65	1.9
5-4-22	7.9	3100	64	2.25

Proceeded for renal transplant

Due to stable ANC (Absolute Neutrophil Count)

Non requirement of blood transfusion,
Absence of infection and bleeding diathesis
Normal cytogenetics which all portends favourable prognosis

Donor: Paternal aunty – 67 years

HLA: 3/6 match

CDC CM: Negative

Screening PRA Class II – Weak positive

PRA by SAB Class I is 19% (Max MFI 1200)

Class II – 0%

Renal transplant on 8-9-22

Induction: not given due to low normal counts for fear of infection

Immunosuppression: TAC/MMF/Steroids.

Date	Hb	TLC	PMN	Platelet
9-9-22	8.9	14700	72%	3.61
13-9-22	8.2	12700	68%	2.78
27-10-22	11.2	6100	74.9%	1.56
26-8-23	15.3	7400	73.2%	2,01

Discharge: Sr. creatinine – 1.4

Follow up 20-8-23: 1.49 – urine routine; Normal BP – 120/80

Case 3

A 29 years old Male 0⁺ patient came with the following complaints like Chronic IgA nephropathy-2017. June 2022- ESRD -HD inducted.

Transplant workup – mother donor-0+

Immunological workup – satisfactory. On April 2023 – Developed pancytopenia.

Lab: Hb -6.9 gm% TC 2400 Platelet – 1.16 lakhs

Bone Marrow Report

Chromosome analysis: Normal karyotype

Then managed with Danazol and erythropoeitin.

Before the renal transplant in Jan 2024,

Lab: Hb – 9.7gm/dl, TLC – 3100, Platelet count – 1.81 lakhs.

Renal transplant on 20-1-24

Induction: Basiliximab

Immunosuppression: Tac/MMF/Steroids

Uneventful postoperative period.

Discharge

Creatinine: 1.2 mg/dl
Hb 10.2 gm/dl : TLC – 4500 Platelet – 1.6 lakhs

Follow up September 2024

Creatinine: 1.2 mg/dl
Hb 14.5 gm/dl; TLC – 7600; Platelet – 1.8 Lakhs

Determinants for safe renal transplant in aplastic anaemia

Favourable factors	Unfavourable factors
Non severe aplastic anaemia Consistent response following treatment for a minimum 3 months. Normal cytogenetics.	Severe Aplastic anaemia requiring transfusions. Persistent platelet count < 1 lakh Persistent neutropenia. Myelodysplasia. Abnormal cytogenetics. Inherited bone marrow failure syndromes.

Points learned from those three cases

Renal transplant can safely be done in non severe aplastic anemia.
Maintenance immunosuppression can safely maintain remission of aplastic anaemia.
Antimetabolites can safely be used without the danger of fall in counts.
Proper evaluation of aplastic anaemia can safely include and exclude the patients for renal transplant.

Dr. T. Rajarajan
Consultant Nephrologist

Renal transplantation in marrow dysfunction: A case series

Renal transplantation in marrow dysfunction: A case series

T. Rajarajan

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