Ask the Experts - Transplantation in HTLV-1 Carriers?
Ask the Experts - Transplantation in HTLV-1 Carriers?
I have not been able to find any reports in the literature concerning transplantation in HTLV-1 carriers. I have heard that the risk of lymphoma would be dramatically increased in such patients, but nobody seems to have published a series. Have you any information on this topic?
With respect to the question you asked about the association of HTLV-1 and T-cell lymphoma in organ transplant recipients, there are a couple of things that should be clarified. First, HTLV-1 seropositivity in the donor is generally considered a contraindication to organ donation -- the prevalence of HTLV-1 in the general US population is very low, less than 0.1%. Organ procurement agencies generally test for this, and if it is positive, the donor is generally not used. We do not routinely test for HTLV-1 in our candidates awaiting transplantation. The incidence of T-cell lymphomas is very low; they make up less than 10% of all posttransplant lymphoproliferative diseases (PTLD), which is present in about 2% to 5% of all transplant recipients. When tested, T-cell PTLD rarely shows HTLV-1 sequences. Thus, in the United States, the association of HTLV-1 with T-cell PTLD lymphomas is exceedingly low and rare. In fact, it could be questioned whether the few case reports are more coincidental rather than causal. In addition, T-cell lymphomas such as mycosis fungoides, which is a cutaneous T-cell lymphoma, has a higher rate of association with HTLV-1. However, in the transplant recipient, this is an unusual presentation for any type of PTLD. I also spoke with Michael Nalesnik, MD, in the Department of Transplant Pathology at the University of Pittsburgh and also a member of this panel, and he does not recall any association of HTLV-1 with T-cell PTLD. I am including several MEDLINE abstracts for your interest. Please feel free to contact me if you have further questions.
Posttransplant T-cell Lymphoproliferative Disorders -- An Aggressive, Late Complication of Solid-Organ Transplantation
Hanson MN, Morrison VA, Peterson BA, et al
Blood. 1996;88:3626-3633
T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43 years). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15 years). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4880 IU/L; median, 1220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.
Posttransplant T-cell Lymphoma. Report of Three Cases and a Review of the Literature
van Gorp J, Doornewaard H, Verdonck LF, Klopping C, Vos PF, van den Tweel JG
Cancer. 1994;73:3064-3072
Background. Although 14% of the malignant lymphomas after organ transplantation are reported to be T-cell lymphomas, only a few cases are described in the literature.
Methods. The authors presented three new cases. They summarized the clinical data and analyzed histologic and immunochemical findings. The presence of Epstein-Barr virus (EBV) and human T-cell lymphoma type 1 (HTLV-1) were investigated. T-cell receptor (TCR) rearrangement was analyzed by Southern blot technique in two cases.
Results. Two of the three lymphomas developed after renal transplantation. One was a T-cell lymphoma of pleomorphic medium-sized cell type and the other was a T-cell lymphoblastic lymphoma; the third T-cell lymphoma was an anaplastic large cell (Ki-1 positive) type that developed after heart transplantation. No association was established with EBV or HTLV-1. A monoclonal TCR rearrangement was found in the two cases that were analyzed. A literature search revealed 22 other cases. Nineteen of the 22 reported cases were peripheral T-cell lymphomas. Almost all lymphomas presented in extra-nodal sites. The time between diagnosis and organ transplantation seemed to be influenced by the type of immunosuppressive therapy. In five cases, EBV was detected in the tumor cells. A monoclonal T-cell receptor rearrangement was found in eight cases and a polyclonal proliferation in one case. Response to therapy was variable, but often poor.
Conclusions. The etiology of posttransplant T-cell lymphomas remains unclear. Similarities with posttransplant B-cell proliferations are the predominant extranodal presentation and the finding that the time of occurrence is influenced by the type of immunosuppression. In contrast with posttransplant B-cell proliferations, only a minority of the cases are associated with EBV. Most tumors appear to be monoclonal. Prognosis is generally poor, but tumor presentation with localized disease might have a somewhat better prognosis.
Adult T-cell Leukemia Developing During Immunosuppressive Treatment in a Renal Transplant Recipient
Tsurumi H, Tani K, Tsuruta T, et al
Am J Hematol. 1992;41:292-294
We report a case of a 32-year-old male, an asymptomatic carrier of human T-cell leukemia virus type 1 (HTLV-1), who underwent a renal transplantation and developed adult T-cell leukemia (ATL) during the course of posttransplant immunosuppressive treatment. He was treated with combination chemotherapies consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, cisplatin, cytosine arabinoside, etoposide, and methyl-prednisolone, without any improvement. Bestrabucil (KM2210), a conjugate of chlorambucil and estradiol, was administered as an alternative therapy; this therapy successfully suppressed his leukemic cell growth, and partial remission was achieved. Posttransplant immunosuppressive therapy with prednisolone, mizoribine, and cyclosporin A might have been the predominant cause of the transition from an asymptomatic HTLV-1 infection to overt ATL. A careful approach is required with HTLV-1 asymptomatic carriers who need organ transplantation followed by immunosuppressive treatment.
I have not been able to find any reports in the literature concerning transplantation in HTLV-1 carriers. I have heard that the risk of lymphoma would be dramatically increased in such patients, but nobody seems to have published a series. Have you any information on this topic?
With respect to the question you asked about the association of HTLV-1 and T-cell lymphoma in organ transplant recipients, there are a couple of things that should be clarified. First, HTLV-1 seropositivity in the donor is generally considered a contraindication to organ donation -- the prevalence of HTLV-1 in the general US population is very low, less than 0.1%. Organ procurement agencies generally test for this, and if it is positive, the donor is generally not used. We do not routinely test for HTLV-1 in our candidates awaiting transplantation. The incidence of T-cell lymphomas is very low; they make up less than 10% of all posttransplant lymphoproliferative diseases (PTLD), which is present in about 2% to 5% of all transplant recipients. When tested, T-cell PTLD rarely shows HTLV-1 sequences. Thus, in the United States, the association of HTLV-1 with T-cell PTLD lymphomas is exceedingly low and rare. In fact, it could be questioned whether the few case reports are more coincidental rather than causal. In addition, T-cell lymphomas such as mycosis fungoides, which is a cutaneous T-cell lymphoma, has a higher rate of association with HTLV-1. However, in the transplant recipient, this is an unusual presentation for any type of PTLD. I also spoke with Michael Nalesnik, MD, in the Department of Transplant Pathology at the University of Pittsburgh and also a member of this panel, and he does not recall any association of HTLV-1 with T-cell PTLD. I am including several MEDLINE abstracts for your interest. Please feel free to contact me if you have further questions.
Posttransplant T-cell Lymphoproliferative Disorders -- An Aggressive, Late Complication of Solid-Organ Transplantation
Hanson MN, Morrison VA, Peterson BA, et al
Blood. 1996;88:3626-3633
T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43 years). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15 years). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4880 IU/L; median, 1220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.
Posttransplant T-cell Lymphoma. Report of Three Cases and a Review of the Literature
van Gorp J, Doornewaard H, Verdonck LF, Klopping C, Vos PF, van den Tweel JG
Cancer. 1994;73:3064-3072
Background. Although 14% of the malignant lymphomas after organ transplantation are reported to be T-cell lymphomas, only a few cases are described in the literature.
Methods. The authors presented three new cases. They summarized the clinical data and analyzed histologic and immunochemical findings. The presence of Epstein-Barr virus (EBV) and human T-cell lymphoma type 1 (HTLV-1) were investigated. T-cell receptor (TCR) rearrangement was analyzed by Southern blot technique in two cases.
Results. Two of the three lymphomas developed after renal transplantation. One was a T-cell lymphoma of pleomorphic medium-sized cell type and the other was a T-cell lymphoblastic lymphoma; the third T-cell lymphoma was an anaplastic large cell (Ki-1 positive) type that developed after heart transplantation. No association was established with EBV or HTLV-1. A monoclonal TCR rearrangement was found in the two cases that were analyzed. A literature search revealed 22 other cases. Nineteen of the 22 reported cases were peripheral T-cell lymphomas. Almost all lymphomas presented in extra-nodal sites. The time between diagnosis and organ transplantation seemed to be influenced by the type of immunosuppressive therapy. In five cases, EBV was detected in the tumor cells. A monoclonal T-cell receptor rearrangement was found in eight cases and a polyclonal proliferation in one case. Response to therapy was variable, but often poor.
Conclusions. The etiology of posttransplant T-cell lymphomas remains unclear. Similarities with posttransplant B-cell proliferations are the predominant extranodal presentation and the finding that the time of occurrence is influenced by the type of immunosuppression. In contrast with posttransplant B-cell proliferations, only a minority of the cases are associated with EBV. Most tumors appear to be monoclonal. Prognosis is generally poor, but tumor presentation with localized disease might have a somewhat better prognosis.
Adult T-cell Leukemia Developing During Immunosuppressive Treatment in a Renal Transplant Recipient
Tsurumi H, Tani K, Tsuruta T, et al
Am J Hematol. 1992;41:292-294
We report a case of a 32-year-old male, an asymptomatic carrier of human T-cell leukemia virus type 1 (HTLV-1), who underwent a renal transplantation and developed adult T-cell leukemia (ATL) during the course of posttransplant immunosuppressive treatment. He was treated with combination chemotherapies consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, cisplatin, cytosine arabinoside, etoposide, and methyl-prednisolone, without any improvement. Bestrabucil (KM2210), a conjugate of chlorambucil and estradiol, was administered as an alternative therapy; this therapy successfully suppressed his leukemic cell growth, and partial remission was achieved. Posttransplant immunosuppressive therapy with prednisolone, mizoribine, and cyclosporin A might have been the predominant cause of the transition from an asymptomatic HTLV-1 infection to overt ATL. A careful approach is required with HTLV-1 asymptomatic carriers who need organ transplantation followed by immunosuppressive treatment.
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