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POST TRANSPLANT LYMPHOPROLIFERATIVE DISORDER
APOLLO HOSPITALS, CHENNAI EXPERIENCE.
Dr.M.K.Mani, Dr.K.C.Prakash, Dr.B.Subbarao, Dr.Rajeev A, Dr.Rajagopalan S,
Dr.Balasubramanian S, Dr.Abhijit Kishore Korane.
Apollo hospitals, Chennai:- 2179 renal transplants.
Live related:- 1980, Cadaver:- 199.
CHANGING PATTERN OF IMMUNOSUPPRESION
PREDNISOLONE+AZATHIOPRINE
1986-1991 (DONAR SPECIFIC TRANSFUSION)
INTRODUCTION OF
1992-2004 CYCLOSPORINE/MMF
USE OF ATG/OKT3 IN HIGH
RISK/RESISTANT REJECTION PATIENTS.
INTRODUCTION OF
2005-2009 TACROLIMUS.
USE OF IL-2 BLOCKERS.
Other malignancies diagnosed(7+PTLD):-
- Adenocarcinoma of rectum(1),
- Carcinoma of uterus(1),
- Carcinoma of cervix(1),
- Carcinoma of breast(1),
- Bronchoalveolar carcinoma(1),
- Carcinoma of tongue(1),
- Kaposi sarcoma(1).
PTLD our experience:-
- We have diagnosed five cases of post
transplant lymphoproliferative disorders.
- This number may not be representative of
actual incidence of the disease.(Patients
were lost for follow up).
LaCasce AS. Post-transplant lymphoproliferative disorders.
Oncologist 2006; 11: 674–680
Ratio observed/expected malignancies in graft recipients
Int J Cancer 60: 183–189, 1995
INCIDENCE OF PTLD
• Incidence of post transplant lymphoproliferative disorder is
approximately 1%.
• The overall incidence of malignancies in Indian transplant recipients
is not known.
• One centre in India reported 30 malignancies (2.1%) in 26 out of
1400.
• Of these post transplant lymphoproliferative disorder accounted for
19 cases (63.3%).
• Crit Rev Oncol Hematol 2005; 56: 71–85.
• Arch Intern Med 2003; 163:1997.
• IndiaJNRT 2(1) 2009 : 94 – 105.
Risk factors for post-transplant malignancies:-
-Viral infections(Epstein-Barr virus, Hepatitis c
virus),
EBV seronegative patients experienced a 10- 76-fold
greater incidence of PTLD when compared with
their seropositive counterparts.
Transplantation 1999; 68:997–1003
Risk factors for post-transplant malignancies.
-Use of the monoclonal
antibody OKT3.
-Calcineurin inhibitors
(tacrolimus).
-Cytomegalovirus-
seropositive donor,
-Younger age at
transplantation. Am J Transplant2004; 4: 222–230
RECEPIENT TRANSPLANT IMMUNOSUPPRES PRESENTATION OF DAIGNOSIS THERAPY/OUTCO
DETAILS DETAILS ION PTLD ME
TREATMENT:-
April 2007:- - MMF,
TRANSPLANT DATE:- Fever, weight loss, Tacrolimus
10th June 2006. anuria. stopped.
DONAR:- Mother. Submandibular Submandibular - 6 cycles of
HLA MATCH:- Haplo lymphnode lymphnode:- CHOP.
identical. ANTIBODIES:- Nil. enlargement. Biopsy showed Non- GRAFT OUTCOME:-
SK, 25yrs, Male. BASIC DISEASE:- CGN. MAINTAINENCE:- USG:- Soft tissue mass Hodgkins lymphoma, - 4 months off
COMORBIDITIES:- Nil. Tacrolimus, MMF, at the hilum of High-grade type. dialysis.
REJECTION:- Steroids. transplant kidney, Bone marrow:- - Developed cross
3rd Jan 2008:- Vascular renal vein thrombosis. Negative for match positive
rejection, CT abdomen:- Soft Lymphoma. vascular
(CX match:-100%) tissue mass at the rejection,
21st Feb 2008:- hilum of transplant received 5 PE,
Cellular and vascular kidney, but later lost the
rejection. retroperitoneal lymph graft.
(5 Plasma exchange) nodes. PATIENT OUTCOME:-
On haemodialysis.
TRANSPLANT DATE:- TREATMENT:-
10th April 1998. ANTIBODIES:- Nil. November 2008:- CT Abdomen:- - Azathioprine
DONAR:- Mother. MAINTAINENCE:- Fever, weight loss, Thickened segment of stopped.
RS, 23yrs, Male. HLA MATCH:- Haplo Cyclosporine, vomiting, abdominal jejunum and ileum. GRAFT OUTCOME:-
identical. Azathioprine,Steroids. pain for 2 months. Laprotomy:- Segment - Worsening of
BASIC DISEASE:- USG:- Thickening of resected. renal functions.
Hereditary Nephritis. the jejunal wall. HP:- Peripheral T cell PATIENT OUTCOME:-
COMORBIDITIES:- Nil. Lymphoma. - Progressive
REJECTION:- 1. (1998) weight loss.
- Expired.
RECEPIENT TRANSPLANT IMMUNOSUPPRES PRESENTATION OF DAIGNOSIS THERAPY/OUTCO
DETAILS DETAILS ION PTLD ME
TRANSPLANT DATE:-
1988.
SR, 18yrs, Male. DONAR:- Mother. 3 months following Lymphnode Biopsy:- TREATMENT:-
HLA MATCH:- Haplo ANTIBODIES:- OKT3. transplant developed Lymphoma. - Immunosuppression
identical. MAINTAINENCE:- lymphadenopathy stopped.
BASIC DISEASE:- CGN. Azathioprine, and worsening of GRAFT OUTCOME:-
COMORBIDITIES:- Nil. Steroids. renal functions. - Graft lost.
REJECTION:- PATIENT OUTCOME:-
Steroid resistant - Expired.
cellular rejection
following transplant,
requiring OKT3.
TRANSPLANT DATE:-
1st Tx:- 1998. USG:- Enlarged TREATMENT:-
(CAN,?BK Virus Kidney. - Immunosuppression
Nephropathy) ANTIBODIES:- 2nd Tx 13 months after CT scan:- stopped.
K,45yrs,Female. 2nd Tx:- 23-5-2006. received Campath, transplant presented Enlarged GRAFT OUTCOME:-
DONAR:- ATG(3 doses). with fever, graft kidney(17cm×10cm), - Graft lost.
1st Tx:- Mother. MAINTAINENCE:- tenderness, azotemia. Retroperitoneal PATIENT OUTCOME:-
2nd Tx:- Unrelated. Sirolimus, Tacrolimus, Lymphadenopathy. - Expired.
HLA MATCH:- 0. Wysolone. Kidney Biopsy:-
BASIC DISEASE:-CIN Dense
COMORBIDITIES:- Lymphoplasmacytic
HCV,CMV,HIV. infilterates.
REJECTION:- Nil.
PREVENTION OF PTLD.
• Patients who are at high risk for the development of
PTLD should be identified before transplantation.
• EBV infection is a significant risk factor and, EBV
serostatus should be determined for all potential
transplant recipients.
• Aggressive supplemental immunosuppression should be
used only in the presence of biopsy-proven acute
rejection.
Treatment:-
• Withdrawal of the antimetabolite and reduce
calcineurin inhibitor dose.
• Use of rituximab, ganciclovir, foscarnet.
• Chemotherapy(CHOP or cyclophosphamide
plus prednisone).
• Radiotherapy.
• Interferon alfa.
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