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The Centre of Excellence for Nephrology Nephrology in apollo

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The Centre of Excellence for Nephrology Nephrology in apollo Powered By Docstoc
					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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