Hematologic Neoplasia in Patients Treated for Hodgkin's Disease

Cn, Coleman; Cj, Williams; Flint, Andrew; Ej, Glatstein; Rosenberg, S A; Hs, Kaplan

doi:10.1056/nejm197712082972303

Cited by 422 publications

(69 citation statements)

References 23 publications

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“…[1][2][3] Our understanding of this serious late effect has evolved over time. Many early studies reported an increased risk of acute leukemia, which has a shorter latency and is associated with the use of alkylating chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors

Bernardo

Weller

et al. 2002

Blood

411

295

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The excess risk of second malignancy after Hodgkin disease is an increasing problem. In light of the long-term data, guidelines for follow-up of survivors of Hodgkin disease need to be redefined. In this study we attempt to analyze the longterm risks and temporal trends, identify patient-and treatment-related risk factors, and determine the prognosis of patients who develop a second malignancy after radiation treatment with or without chemotherapy for Hodgkin disease. Among 1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies and 18 third malignancies were observed. With a median follow-up of 12 years, the relative risk (RR) and absolute excess risk of second malignancy were 4.6 and 89.3/10 000 person-years. The RR was significantly higher with combined chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0, P ‫؍‬ .015). The risk increased with increasing radiation field size (P ‫؍‬ .03) in patients who received combined modality therapy, and with time after Hodgkin disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second malignancy per person per year. The 5-year survival after development of a second malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung cancer. The excess risk of second malignancy after Hodgkin disease continues to be increased after 15 to 20 years, and there does not appear to be a plateau. Our analysis suggests that the risk may be reduced with smaller radiation fields, as are used in current trials of abbreviated chemotherapy and limitedfield radiation therapy.

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Section: Introductionmentioning

confidence: 99%

Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors

Bernardo

Weller

et al. 2002

Blood

411

295

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“…Results were apparently good, but unfortunately, a significant incidence of leukemia and sarcoma developed in these patients and the treatment was essentially abandoned (23). However, none of 320 patients with Hodgkin's disease treated with TLI has shown a hematologic neoplasm in a 10-year followup (24). Reasons for the marked difference in the tumorigenicity of the two radiation regimens is unclear but may be related to differences in fractionation, dose per fraction, ports, and megavoltage versus kilovoltage xrays.…”

Section: Discussionmentioning

confidence: 99%

Total lymphoid and local joint irradiation in the treatment of adjuvant arthritis

Schurman

Hirshman

Strober

1981

Arthritis & Rheumatism

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Total lymphoid irradiation (TLI) with 3,400 rads delivered in 17 divided doses, 600 rads at local paw irradiation in 3 divided doses, or both TLI and local irradiation were used to treat Lewis rats with adjuvant arthritis. Either TLI alone or local paw irradiation modestly reduced the severity of arthritis compared to a control group (P < 0.05). TLI treated animals had more initial suppression of inflammation. Adjuvant rats treated with a combination of both TLI and local paw irradiation had a profound and long lasting reduction in inflammation and permanent arthritis (P < 0.001).Immunosuppression in one form or another is well known to be beneficial in the treatment of inflammatory polyarthropathies. The lymphocyte is integrally involved in the histopathology of all forms of inflammatory arthritis in humans and animals. Alkylating agents which are known to destroy lymphocytes and thoracic duct drainage which mechanically depletes lymphocytes are associated with a decrease in synovitis in patients with rheumatoid arthritis (1). We reasoned, therefore, that the technique of selective irradiation (TLI) used to treat Hodgkin's disease might prove to be a valuable treatment for inflammatory synovitis since this regimen produces long lasting immunosuppression and T lymphocytopenia (2). Local irradiation of pigmented villonodular synovitis and intraarticular injection of radionuclides have met with some success as alternatives to surgical synovectomy (3-5). We investigated how local irradiation of inflamed joints would compare to TLI in suppressing inflammatory arthiritis in an animal model. This report describes the results of TLI and local joint irradiation separately and in combination in adjuvant arthritis of rats. It was found that either TLI or local joint irradiation is therapeutic by itself, but the combination of both modalities is substantially more effective than either alone. MATERIALS AND METHODSExperimental scheme. Adult inbred Lewis rats weighing 350 to 500 gm were injected with 1.0 mg of Mycobacterium butyricum suspended in medium grade oil at a concentration of 10 mg/ml in the subcutaneous aspect of the left hind paw (LHP), in a procedure similar to that reported by Chang (6). On the seventeenth day after inoculation of the LHP, animals that developed arthritis in one or more of the remaining three paws and had a minimum arthritis rating score of three (see "Scoring of joints") were divided into four groups of approximately 4 animals each. Groups were chosen so that there was a similar distribution of arthritis, and the average score of each group was similar at the start. All treatment regimens started on the seventeenth day after adjuvant inoculation. One group served as controls and received no irradiation. A second group was given a total of 3,400 rads of TLI in divided doses of 200 rads/day on a 5-day-a-week basis over a period of 24 days. A third group of animals received both 3,400 rads of TLI and 600 rads to each of the four paws. The paws were irradiated with 200 rads/day for 3 days starting ...

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“…In addition, accurate delineation of the involved areas makes it possible to tailor treatment to the specific needs of the patient who may be spared the hazards of overtreatment and vulnerabilty to growth retardation, endocrine dysfunctions, and emergence of second malignancies. [27][28][29][30] Precise surgical staging, the advocates say, makes restaging for the assessment of therapy easier and patients who need more therapy can be identified earlier and treated properly. 31 Surgical staging has contributed to a great deal of understanding about the patterns of disease spread.…”

Section: Discussionmentioning

confidence: 99%

Staging Laparotomy and Splenectomy for Hodgkin’s Disease in Children—Reassessment

et al. 1982

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Hematologic Neoplasia in Patients Treated for Hodgkin's Disease

Cited by 422 publications

References 23 publications

Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors

Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors

Total lymphoid and local joint irradiation in the treatment of adjuvant arthritis

Staging Laparotomy and Splenectomy for Hodgkin’s Disease in Children—Reassessment

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