Effect of azathioprine on the chromosome complement of human bone marrow cells

Jensen, Mogens Krogh

doi:10.1002/ijc.2910050119

Cited by 65 publications

(12 citation statements)

References 20 publications

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“…28 Interestingly, 16 of the 19 patients had received azathioprine which has been shown to be mutagenic in patients with rheumatic diseases. 31 In contrast to post-transplant lymphoproliferative disorder (PT-LPD), where immunosuppression followed by EBV-infection is causative, 5 PT-AML could rather be a direct consequence of drug toxicity. In a recent report, Leblond et al 32 showed that EBV-negative PT-LPDs also have a latency of 5 years with most patients receiving azathioprine.…”

Section: Frequency Pathogenesis and Latencymentioning

confidence: 99%

Post-transplant acute myeloid leukemia (PT-AML)

et al. 1999

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Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, Ͻ1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: −7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), Gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.

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Section: Frequency Pathogenesis and Latencymentioning

confidence: 99%

Post-transplant acute myeloid leukemia (PT-AML)

et al. 1999

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“…The excess is due almost entirely to the incidence of reticulum cell sarcoma, which was 350 times more common than expected. The following hypotheses have been proposed to explain the high incidence of neoplasms in transplant recipients: (1) chromosome breakage secondary to immunosuppressant drugs, especially azathioprine (Jensen, 1970); (2) continual antigenic stimulation of the homograft recipient (Walford, 1966;Armstrong et al, 1970); (3) proliferation of oncogenic viruses (Schwartz and Andre-Schwartz, 1968); and (4) depression of the host's immunological surveillance apparatus (Dent et al, 1968;Hellstrom and Hellstrom, 1969).…”

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confidence: 99%

Cerebral reticulum cell sarcoma after multiple renal transplants

Barnett¹,

Schwartz²

1974

Journal of Neurology, Neurosurgery & Psychiatry

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SYNOPSIS A case is reported of a 34 year old white male with chronic renal failure secondary to glomerulonephritis who received four renal transplants over a period of five years. He died 25 months after the fourth transplant. Necropsy revealed a reticulum cell sarcoma-microglioma of the brain. The possibility that multiple transplants may have had a synergistic effect in the development of a malignant cerebral lymphoma in this patient is briefly discussed in the light of the current theories concerning the pathogenesis of the tumours in transplant recipients and in the context of the present therapeutic approach to graft rejection.The high incidence of malignancies in patients who have undergone transplantation procedures is now well known (Penn, 1970;Schneck and Penn, 1971;Hoover and Fraumeni, 1973). The prognosis of patients receiving multiple transplants, however, has not been clearly established, although there is some preliminary evidence suggesting that the risk of cancer other than lymphoma is somewhat higher in these patients than in those receiving a single transplant (Hoover and Fraumeni, 1973). In a series of 37 tumours arising in renal homograft recipients. Penn (1970) briefly describes three cases of multiple transplants; the brain was not implicated in these patients. Schneck and Penn (1971) CASE REPORTThe patient was a 34 year old male who first came to medical attention because of an attack of acute glomerulonephritis at the age of 15 years. He had proteinuria and red and white cell casts in the urine, but his renal function studies were within normal limits and remained so for the next 10 years during multiple evaluations at the Stanford University Medical Center. Then, over the course of the subsequent year, he developed azotaemia, malignant hypertension, and ensuing chronic renal failure. He began to be maintained on haemodialysis at the age of 26 years; this was continued for three years until he received his first kidney transplant. The transplant was from a cadaver donor, functioned poorly for five weeks, and was rejected. Microscopic examination of the kidney showed acute rejection with infarction. Dialysis was resumed for another year until, at the age of 30 years, he received a second renal transplant from a living, related donor (his brother); it was rejected almost immediately, and microscopic examination confirmed a hyperacute rejection reaction with glomerular capillary fibrin thrombi. Haemodialysis was resumed until, at the age of 32 years, he received his third kidney transplant. This was from a living but non-related donor, and never functioned. Open biopsy revealed glomerular capillary thrombi with extensive cortical necrosis. The transplanted kidney was removed after a few days and a fourth transplant, from a cadaver donor, was inserted in its place. This kidney functioned adequately for 18 months but was then removed be-

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“…For example, this consideration might account for some disparate reports, such as the positive findings of Jensen (1967), who studied bone marrow, andVoorhees et al (1969), who found n o chromosome damage in lymphocytes. Attention is also drawn to this possibility in a recent report of the cytogenetic effects of azathioprine by Jensen (1970). However, our studies shed no light on possible different results due to variation in drug dose or route of administration.…”

Section: Discussionmentioning

confidence: 74%

Human mitotic and meiotic chromosome damage following in vivo exposure to methotrexate

1971

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Mitotic chromosome damage was found in bone marrow cells but not in cultured lymphocytes or fibroblasts from a patient receiving methotrexate for treatment of psoriasis. No meiotic chromosome damage was detected in a testicular biopsy taken at the same time. These findings suggest that a full, definitive evaluation of human chromosome damage following drug exposure may require examination of several different tissues.

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Effect of azathioprine on the chromosome complement of human bone marrow cells

Cited by 65 publications

References 20 publications

Post-transplant acute myeloid leukemia (PT-AML)

Post-transplant acute myeloid leukemia (PT-AML)

Cerebral reticulum cell sarcoma after multiple renal transplants

Human mitotic and meiotic chromosome damage following in vivo exposure to methotrexate

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