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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM THE ARAB WORLD Table of Contents   
Year : 2006  |  Volume : 17  |  Issue : 3  |  Page : 408-414
Incidence and Types of Malignancies in Renal Transplant Recipients in Iraq


1 Al-Karama Teaching Hospital - Kidney Transplantation Center, Baghdad, Iraq
2 Medical City Kidney Transplantation Center, Baghdad, Iraq

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   Abstract 

We retrospectively reviewed the records of 273 renal transplant recipients who received allograft transplants between 1994 and 2004 and recorded the incidence and types of de novo malignancies that developed in these patients. The study was carried out at the Al-karama and Al-rasheed kidney transplant centers in Baghdad, Iraq. A total of 16 patients developed malignancies. The tumors included Kaposi's sarcoma (KS) in eight patients, squamous cell carcinoma (SCC) in four, basal cell carcinoma (BCC) in two and both renal cell carcinoma of the allograft and brain tumor in one patient. Thus, KS was the most common malignancy encountered in our series, with a prevalence of 2.9%, followed by SCC observed in 1.5% and BCC found in 0.7 % of the patients. The average latency period between transplantation and development of malignancy was 6.5 months for KS, 3.0 months for SCC and 8.5 months for BCC. To our knowledge, this is the first long-term follow-up study for malignant complications identified in kidney recipients in Iraq.

Keywords: Malignancies, Renal Transplantation, Iraq.

How to cite this article:
Altaee IK, Jaleel NA, Aljubury HM, Alshamaa IA, Gazala S. Incidence and Types of Malignancies in Renal Transplant Recipients in Iraq. Saudi J Kidney Dis Transpl 2006;17:408-14

How to cite this URL:
Altaee IK, Jaleel NA, Aljubury HM, Alshamaa IA, Gazala S. Incidence and Types of Malignancies in Renal Transplant Recipients in Iraq. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2020 Jan 26];17:408-14. Available from: http://www.sjkdt.org/text.asp?2006/17/3/408/35777

   Introduction Top


Renal allograft recipients have an increased incidence of post-transplant malignancies, particularly cancer of the skin, lymphoma and Kaposi's sarcoma. Conversely, malignancies commonly encountered in the general popu­lation, such as carcinoma of the prostate, breast, lung, colon and invasive uterine cervical carcinomas, do not show a higher frequency of occurrence in renal recipients compared to the general population. [1],[2]

Epidemiological studies show a 49-fold increase of non-Hodgkin's lymphoma (NHL), a 29-fold increase in lip cancers and a 400-fold increase in Kaposi's sarcoma (KS), among renal transplant recipients when compared with age-matched controls in the general population. [1],[3]

The incidence of malignancies increases with longer duration of follow-up in these patients.[4]

Post-transplant malignancies have some unusual features, which differ from those found in the general population.[5] They include the following: more aggressive in nature, occur in a younger age group, show high frequency of KS, squamous cell carcinoma (SCC) and NHL, reversal of the normal ratio of basal cell carcinoma (BCC) to squamous cell carcinoma which is 5: 1 in the general population and 1: 1.8 in the transplant population. Also, skin malignancies may recur and involve more than 100 sites in a single patient, especially when there are wide spread pre-malignant skin lesions.

Each tumor type has a specific latency period (LP) i.e. the period between the time of renal transplantation and the clinical appearance of the tumor. KS has an average LP of 22 months, NHL has an average of 33 months, and SCC and BCC have an LP of less than one year. Vulval and perineal carcinomas have the longest LP with an average of 113 months.

The pathogenesis of cancers in allograft recipients include:

a) Immunodeficiency state, which directly influences the risk of cancer

b) Oncogenic viral infection or reactivation of latent virus in the recipients. The principal neoplasms and their associated viruses are lymphoproliferative disorders due to Epstein- Barr virus (EBV), KS due to human herpes virus-8 (HHV-8), skin cancers due to human papilloma virus, and hepatitis B virus (HBV) and hepatitis C virus (HCV) that are associated with hepatocellular carcinoma. [5],[6]

c) Intensive immunosuppresion with various drugs used for the induction and maintenance following transplantation as well as the duration of the treatment with these agents influence both the incidence and the type of cancer; e.g. cyclosporine (CsA) accelerates the development of KS, skin cancers and lymphoproliferative disorders, while azathioprine (Aza) accelerates skin cancers. The combination of tacrolimus and mycophenolate mofetil (MMF) has been associated with an additional rise in the incidence of cancer.[6] Intensive immunosuppresion causes direct damage to DNA which, combined with continuous antigenic stimulation, can lead to cancer.[5]

d) HLA-matching also has a role in the pathogenesis of post-transplant malignancies; recipients with HLA-A3, B27 and DR7 are more susceptible to skin cancers, those with HLA- B51 are more susceptible to KS, while HLA-11 has a protective effect.[7]

According to Stallone et al,[8] the incidence of skin tumors in kidney recipients on dual immunosuppressive agents (Aza + predni­solone) is 3% and their average LP is 24 months, while those on CsA and prednisolone have an incidence of 10% and a LP of 10 months. In patients on triple immunosuppresion (CsA, Aza, and prednisolone), the incidence does not change but the LP is reduced to nine months. This indicates that CsA is more carcino­genic than azathioprine, while combination therapy will shorten the LP and accelerate the onset of malignancies.

In Iraq, an active renal transplantation program was started in 1973 and since then, these surgeries are routinely performed in many centers in Baghdad, the capital. The one, five and 10-year patient and graft survival rates in most of these centers are comparable to what has been published in the literature.[9]

The aim of this retrospective follow-up study is to evaluate the incidence and types of malignancies observed in renal allograft recipients and their outcome in Iraq.


   Patients and Methods Top


The records of 273 kidney recipient patients from Al-karama and Al-rasheed kidney transplant centers were reviewed retrospectively and analyzed with particular reference to age, sex, type of donor, nature of immunosuppression used, type of tumor, latency period of tumor and the outcome in each patient. The period of follow-up ranged from 1994 to 2004.

All, except eight of the study patients, were recipients of primary renal transplantation. Eight patients were recipients of second allografts. The male (238) to female (35) ratio was (6.8:1) and their age at the time of transplantation varied from 15 to 59 years with an average of 37 years. The follow-up period after transplantation ranged from 1 month to 10 years.

A total of 230 patients (84.2%) had live related donor (LRD) transplants while 27 (9.9%) had transplants from live unrelated donors (LURD). Sixteen patients (5.9%) received kidneys from live emotionally related donors (LERD).

The immunosuppresion protocol was modified over the study period. The early protocol included usage of Aza, CsA and prednisolone, while recently MMF and tacrolimus have been used in addition to basiliximab (simulect) in induction therapy. MMF was introduced in the year 2000, simulect in the year 2002 and tacrolimus in 2004.


   Results Top


A total of 16 patients in our series (5.9%) had post-renal transplant malignancies. KS was the most common type, encountered in eight patients (2.9%) followed by SCC seen in four patients (1.5%) and BCC, seen in two patients (0.7%). Both allograft renal cell carci­noma and cerebral tumors were observed in one patient (0.4%). All our patients had normal graft function at the time of diagnosis of malignancy, and all were negative for the HIV antibody.

[Table - 1] shows the type of malignancy in relation to the immunosuppressive protocol used, the LP, and the outcome of malignancy in each patient. In all cases, a triple drug immuno­suppressant regimen, including prednisolone, Aza and CsA was used. The patient with the brain tumor was on dual therapy (prednisolone and Aza) at the time of diagnosis of the tumor. One of the patients with KS received basiliximab at induction in addition to the triple therapy.

The average LP for KS in our patients was 6.5 months, 3.0 months for SCC, and 8.5 months for BCC.

Out of the eight cases of KS, three presented in stages I and II. Here, the lesions were localized to one or more upper or lower limbs [Figure - 1]. Three other patients presented in stage III, where the lesion involved the viscera and/or lymph nodes. The remaining two patients with KS presented in stage IV, with involvement of the skin, viscera, lymph nodes, oropharynx and the testes [Figure - 1],[Figure - 2]. In all cases, the diagnosis was con­firmed by histopathological examination.

Recipients with SCC (4 patients) and BCC (2 patients) had their lesions on the sun-exposed areas. One of them had multiple lesions of SCC, which involved about 10 sites [Figure - 3].

Allograft renal cell carcinoma, which is a very rare condition, was found in one of our patients, who developed the tumor three years after transplantation from a LURD. Graft nephrectomy was performed and the diagnosis was confirmed histopathologicaly [Figure - 4].

One patient in our series who developed signs of increased intracranial pressure seven years after transplantation had a brain tumor detectable by CT-scan. He was referred to the neurosurgery center and died there. No histopathology was available in this patient.


   Discussion Top


Data from several large renal transplant programs show an overall incidence of cancer ranging from 4 -18%. In our study, the inci­dence was 5.9%, which is comparable to the literature.[10] The majority of malignancies reported are de novo neoplasms, although a very small number of tumors may be trans­planted accidentally from the donor.[4]

In our series, the average LP for KS was 6.5 months, which is less than that reported in the literature, while those for SCC and BCC were comparable to the average of less than one year often reported in the literature. In both SCC and BCC, the short LP can be attributed to aggressive immunosuppression.

KS was the most common type of malignancy in our series, 2.9%, which is equivalent to almost 50% of malignancies we encountered. Its reported incidence in literature ranges from 0.4% in USA (according to CTTR report), to 6% in Saudi Arabia [11] and 13.3% in Sudan, which is the highest reported incidence. [12] It is common in people of Arab, Jewish, Italian, and Mediterranean ancestry.[5]

[Table - 2] shows the clinical staging of patients with post-transplant KS. [13] Worldwide, 60% of KS is of the non-visceral mild type; 98% of the patients only have skin involvement and two percent of the patients have involve­ment of the mucosa of the mouth, larynx, pharynx and nose. The remaining 40% is a visceral aggressive form, involving the gut, lungs, lymph nodes and, rarely, liver and genitalia.[5],[14] The mainstay of treatment of post-transplant KS is reduction or disconti­nuation of immunosuppressive therapy, while other modalities include surgical excision, radiotherapy and chemotherapy.[12] More recently, sirolimus has been used in the treatment of KS.[8]

The overall prognosis in our patients with stages I and II KS was good. They were cured without recurrence of the lesions [Table - 1]. Two of our patients with stage III and one with stage IV died because of the severity of the disease and irreversible graft rejection due to discontinuation of the immunosuppressive medication. One patient with stage III returned to hemodialysis and received a second graft after one year's treatment for KS. He is doing well on a modified, low dose immunosuppressive regimen since 1996.

Among skin cancers, SCC is more common than BCC and occurs on the exposed areas, mainly head, neck, and upper extremities. It has an aggressive course. The incidence of SCC (1.5%) is about double that of BCC (0.7%). They constituted 25% and 12.5% of malignant lesions seen in our series, respect­ively. This is comparable to the ratio mentioned in the literature. One patient had recurrent lesions of SCC at different sites of his face, lips and hands; moreover, he had one lesion of BCC on his nose. Histopathology revealed hyperelastosis of the skin. This is a pre­malignant condition contributing to the develop­ment of other factors involved in the patho­genesis of malignancy in post-transplant recipients.[5] This patient has been doing well with a normal graft function since 1998.

Renal cell carcinoma in renal allograft recipients usually occurs in the native kidneys, generally as a complication of the primary disease of the native kidneys. Its incidence is 9%. Its occurrence in the allograft patient is very rare and seen in only 0.4% of patients.[1][,5],[10] In our series, one patient developed renal cell carcinoma of the allograft three years after transplantation. The diseased kidney was excised and the patient returned to hemo­dialysis. Six months later, he underwent a second transplantation from another LURD. This patient has been alive since 1999 and possesses good renal function. To our knowledge, this condition is very rare and is the only recorded case in Iraq.

Penn recommends waiting for at least two years before subjecting a patient with known malignancy to renal transplantation. While this period is appropriate for most malig­nancies, those with a slow recurrence rate e.g. renal cell carcinoma and in situ carcinoma of various organs may be transplanted after a shorter waiting period. [15]


   Conclusions and Recommendations Top


a) KS is the most common post-renal transplant malignancy in our area, followed by SCC and BCC.

b) Avoid over immunosuppression, using the least possible immunosuppressive medication.

c) Avoid undue exposure of uncovered areas of skin of the transplant patients to sunlight.

d) A pre-transplant viral screen and control of the viral infection is strongly recommended.

e) Diligent follow-up of the recipients at regular intervals is essential for early detection of the tumor.

 
   References Top

1.Penn I. Immunosuppressive agents, Immunodeficiency state & malignancy. In: Librman R and Mukherjee A. eds. RG Landes Co. Principles of drug development in transplantation and autoimmunity 1996; 7:93-102.  Back to cited text no. 1    
2.Penn I. Primary kidney tumors before & after renal transplantation. Transplantation 1995;59:480-5.  Back to cited text no. 2    
3.Penn I. Porat G. Central nervous system lymphomas in organ allograft recipients. Transplantation 1995;59:240-4 .  Back to cited text no. 3    
4.Penn I. Transmission of cancer with donor organs. Transplant Proc 1988;20:739-40.  Back to cited text no. 4    
5.Penn I. Malignancy in renal transplant recipients. Saudi J Kidney Dis Transplant 1996;7(1):1-5.  Back to cited text no. 5    
6.Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. New Engl J Med 2005;352: 1371-3.  Back to cited text no. 6    
7.Qureshi BH. Skin cancer and HLA association in renal transplant recipients. Saudi J Kidney Dis Transplant 1996;7(4): 394-7.  Back to cited text no. 7    
8.Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal transplant recipients. New Engl J Med 2005;352(13):1317-23.  Back to cited text no. 8    
9.Al-Taee I, Al-Shamaa I. Long term follow­up of renal transplant patients - a single center experience in Iraq. Saudi J Kidney Dis Transplant 2005;16(1):40-5.  Back to cited text no. 9    
10.Penn I. Neoplastic complications of transplantation. Semin Respir Infect 1993;8: 233-9.  Back to cited text no. 10    
11.Al - Sulaiman MH, Al- Khader AA. Kaposi's sarcoma in renal transplant recipients. Transplant Sci 1994;4:46-60.  Back to cited text no. 11    
12.Sabeel AI, Qunibi WY, Al-furayh OA, Almeshari K. Kaposi's sarcoma in Sudanese renal transplant recipients: a report from a single center. J Nephrol 2003;16:412-6.  Back to cited text no. 12    
13.Mendez JC, Paya CV. Kaposi's sarcoma and transplantation. Herpes 2000;7(1):18-­23.  Back to cited text no. 13    
14.Shaaban AA. Incidence and types of malignant tumors in renal transplant recipients. Saudi J Kidney Dis Transplant 1998;9(2):116-22.  Back to cited text no. 14    
15.Penn I. Kaposi's sarcoma in immuno­suppressed patients. J Clin Lab Immunnol 1983;12:1-10.  Back to cited text no. 15    

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Correspondence Address:
Iqdam K Altaee
Department of Urology and Kidney Transplantation, Al-Karama Teaching Hospital, P.O.Box 3712, Elwiya, Baghdad
Iraq
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    Figures

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    Tables

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