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The Centre of Excellence for Nephrology Nephrology in apollo

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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.
THANK YOU

								
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