Relative Risk Of Leukemia Research Articles

Development of acute myelocytic leukemia in patients with Crohn's disease

In our hospital within one year two patients with Crohn's disease were seen who developed an acute myelocytic leukemia. A review of the literature reveals eight previously reported patients with both Crohn's disease and leukemia. Six of the reported 10 patients have had acute myelocytic leukemia and, interestingly, three of them, including our two patients, have shown monocytic differentiation (FAB type M4). It has been suggested that the relative risk of leukemia, especially acute myelocytic leukemia, is increased in patients suffering from ulcerative colitis. More data of patients with Crohn's disease and acute leukemia are needed to evaluate the possible association between these diseases.

A comparison between the risks of childhood leukaemia from parental exposure to radiation in the Sellafield workforce and those displayed among the Japanese bomb survivors

The cases of childhood leukaemia found near the Sellafield plant and those observed in the offspring of the Japanese bomb survivors are analysed using a relative risk model. The leukaemia relative risk coefficients for total paternal (whole-body) pre-conception exposure for the Sellafield children are found to be about 50 to 80 times higher than the (gonadal) coefficients applying to the offspring of the bomb survivors. This difference is statistically significant, and in particular the risk coefficients for the Sellafield cohort are significantly positive, unlike those for the Japanese. If the assumption is made that the excess relative risk estimated from the Sellafield data lasts for the whole of the life of the offspring, the apparent population leukaemia risk to the first-generation offspring (for an England and Wales population) would be between 4% Sv-1 and 5% Sv-1. On the more likely assumption that the relative risk falls off in the same way as has been observed for leukaemias in children directly exposed to radiation, the risk would then be reduced to about 0.5%-1.5% Sv-1. Such data as exist on the degree of heritability of susceptibility to cancer suggest that the risk to all generations could be about double this figure. The differences between the apparent pre-conception exposure risks in these two groups are discussed and several possible explanations for the findings near the Sellafield plant, other than pre-conception radiation exposure, are presented.

Impact on second malignancy risk of the combined use of radiation and chemotherapy for lymphomas

The risk of a second malignancy was determined for 999 patients given primary treatment using chemotherapy only, radiation therapy only, or both for Hodgkin's Disease or a non-Hodgkin's lymphoma at Duke University Medical Center between 1970 and 1981. The incidence, 10-year actuarial risk, and relative risk of developing an acute leukemia, solid tumor, or second lymphoma were determined by treatment modality and initial lymphoma type. Among the 313 Hodgkin's disease patients, the acute leukemia actuarial risk was 2.0% after chemotherapy, 1.4% after radiation therapy, and 0.9% after combined treatment with chemotherapy and radiation therapy. Their relative risk for acute leukemia was 51.3 overall (95% confidence interval [CI] 13.8 to 131.8) and was elevated in each treatment group. Among the 686 non-Hodgkin's lymphoma patients, the acute leukemia actuarial risk was zero after radiation therapy, 4.6% after chemotherapy, and 4.5% after the combined treatment, again not significantly different between treatment groups. The leukemia relative risk was 10.6 (95% CI 3.4 to 24.8) in the chemotherapy and 11.9 (95% CI 3.2 to 30.6) in the combined treatment group. Among both the Hodgkin's disease and non-Hodgkin's lymphoma populations, the combined treatment group had a lower actuarial risk for solid tumors than either the chemotherapy or radiation therapy group (P less than 0.02). Solid tumor actuarial risk did not differ significantly between the chemotherapy and radiation therapy groups. Hodgkin's disease patients had a solid tumor relative risk that was elevated significantly after radiation therapy (6.5; 95% CI 2.4 to 14.0) and to a lesser extent after chemotherapy (2.6; 95% CI 0.8 to 6.1) or combined treatment (1.7; 95% CI 0.2 to 6.0). Solid tumor relative risk among non-Hodgkin's lymphoma patients was 0.3 for the combined treatment, 0.8 for the chemotherapy, and 1.0 for the radiation therapy group. None of the Hodgkin's disease patients developed a non-Hodgkin's lymphoma. This study found no significant difference in leukemia risk among lymphoma patients treated with chemotherapy and the combined treatment. It also found that the overall risk of a second malignancy is no higher after treatment with the combined therapy than with chemotherapy or radiation therapy alone.

Acute nonlymphocytic leukemia after treatment of small cell lung cancer

From 1977 to 1982, 377 patients with small cell lung cancer were treated at Vanderbilt University Medical Center. All patients received combination chemotherapy consisting of cyclophosphamide, doxorubicin, and vincristine (CAV) with or without methotrexate, etoposide, and/or hexamethylmelamine. Thoracic and/or prophylactic cranial irradiation was administered to 159 (42 percent) and 192 (51 percent) patients, respectively. Acute nonlymphocytic leukemia was observed in two patients at 22 and 81 months from the start of therapy. The relative risk of leukemia was 154 (95 percent confidence limit, 38 to 293). A Kaplan-Meier estimate of the cumulative probability of leukemia was 1.9 ± 1.4 percent seven years after the start of treatment. The relative risk of leukemia is significantly increased in this group of patients (p <0.0001). Acute nonlymphocytic leukemia is a long-term complication of small cell lung cancer therapy.

Inflammatory bowel disease and leukemia

In a review of a large number of patients with inflammatory bowel disease, leukemia was observed in five patients with chronic ulcerative colitis and in two patients with Crohn's disease. In ulcerative colitis patients, there were three cases of acute myelocytic leukemia and one case each of acute lymphoblastic leukemia and chronic granulocytic leukemia. In Crohn's disease patients, there was one case each of chronic granulocytic leukemia and chronic lymphocytic leukemia associated with thrombocythemia. Sixteen other cases of leukemia have been reported to date in inflammatory bowel disease. All types of leukemia, but particularly acute myelocytic leukemia, have been described. There has been no single common feature as to type (whether ulcerative colitis or Crohn's disease), extent and course, or medical and surgical treatment of the bowel disease. The relative risk of leukemia in patients with ulcerative colitis was 5.3 [95% confidence interval 1.7 to 12.3 (P less than 0.01)] and of acute myelocytic leukemia 11.4 [95% confidence interval 2.3 to 24.9 (P less than 0.01)]. Our data on patients with Crohn's disease were not sufficient to assess the statistical significance of leukemia in this disease. This study suggests that there may be an increased risk of leukemia, particularly acute myelocytic leukemia, in ulcerative colitis. The causal relationship, if any, remains undetermined.

Second Primary Cancers Following Treatment of Hodgkin's Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;

A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was conducted. This report describes 2,591 patients with HD diagnosed in 1940-75 and presents an analysis of follow-up findings through 1978. Seventy-four second primary cancers (excluding basal cell and squamous cell cancers of the skin and in situ carcinomas of the cervix uteri) were observed 1 year or more after diagnosis of HD, including 21 leukemias. Twenty leukemias occurred after chemotherapy. The relative risk (RR) of leukemia after intensive chemotherapy with or without radiotherapy was 136 relative to general population incidence rates. In the subgroup with both intensive chemotherapy and intensive radiotherapy, the RR of leukemia was 125. Both RR estimates differed significantly from unity. The RR of cancers other than leukemia 10 years or more after intensive radiotherapy relative to no intensive therapy was 19.5 (95% confidence limits: 4.8-80).

Second Cancers After Radiotherapy and Chemotherapy for Early Stages of Hodgkin's Disease2

In a population of 334 patients treated for Hodgkin's disease by the European Organization for Research and Treatment of Cancer between 1964 and 1971, 21 patients with second primary cancers (SC) were observed: 4 patients with acute leukemias, 3 with non-Hodgkin's lymphomas, and 14 with solid tumors. Time to SC ranged from 2 to 16 years after initial treatment. The relative risk (RR) of acute leukemia for the patients with Hodgkin's disease as compared to the general population was 40 (P less than .001). The RR of leukemia in patients treated by polychemotherapy--mechlorethamine, vincristine, procarbazine, and prednisone--for relapse was 300 (P less than .001). However, the RR of leukemia for those patients who did not experience a relapse was 14 (not significant). The RR of other SC in the overall group was 3.76 (P less than .001). For patients whose relapses were treated by polychemotherapy the RR of SC, leukemia excepted, was 26 (P less than .001), whereas for patients not treated by polychemotherapy for relapse the RR was slightly increased (RR = 3.67; P = .027). The cumulative proportions of acute leukemia at 10 years were 0.7% in the "no-relapse" group and 2.7% in the polychemotherapy group. The cumulative proportions of other SC at 10 years was 1.3% in the no-relapse group, 7.2% in the group of patients not treated by polychemotherapy after relapse, and 8.4% in the polychemotherapy group. The first important risk factor for developing an SC was polychemotherapy, and the second was age over 40 years. These data suggest that combination chemotherapy may be responsible for both acute leukemias and other SC.

Leukemia and Other Cancers After Radiotherapy and Chemotherapy for Hodgkin's Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;

A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was begun in 1976. This report describes 1,553 patients diagnosed with HD in 1940–75 and presents an analysis of follow-up findings through 1976. Twenty-seven cancers (excluding basal cell and squamous cell carcinomas of skin, trichoepitheliomas, and in situ carcinomas of cervix uteri) were observed 1 year or more after diagnosis of HD, including 6 leukemias. The relative risk (RR) of leukemia in patients treated with intensive chemotherapy with or without radiotherapy relative to general population incidence rates was 140 (95% confidence limits: 50,300). In the subgroup treated with both intensive radiotherapy and intensive chemotherapy, the RR of leukemia was 270 (95% confidence limits: 56,800). No leukemia occurred after treatment with intensive radiotherapy without chemotherapy. For cancers other than leukemia and for non-HD lymphomas, RR were generally not significantly different from the null value one.

Cumulative genetic damage in children exposed to preconception and intrauterine radiation.

Using a mathematical model and newly developed computer software, the data from the Tri-State Leukemia Survey involving different combinations of radiation exposures to the father and mother prior to conception and to the mother during pregnancy were analyzed. The hypothesis that radiation exposure produces genetic damage which may be expressed in the child both as indicator disease and as leukemia was tested. The genetic damage was estimated in terms of the proportion affected by a given exposure. The relative risk of leukemia and certain other indicator diseases among those "affected" could then be estimated. The results were obtained by direct minimization of the total chi-square. The results show that there are at least two distinguishable risk groups, one group with lower (one or two exposures), and the other group with higher (two or three) radiation exposures. The estimates for the proportion affected are 0.13 and .04 for the lower and higher exposure groups, respectively. The relative risks of leukemia and indicator diseases are 25.0 and 5.0, respectively. The 95% confidence intervals for the proportion affected in the lower and higher exposure categories are (.0075, .02) and (.028, .055), respectively, and for the relative risk of leukemia are (16.0, 35.0). These results have confirmed and extended the findings of our preliminary report published in the Journal of the American Medical Association in May 1977.

Serum haptoglobin type and leukemia: an association with possible etiological significance.

Haptoglobin type has been determined in 79 subjects with leukemia of various types, and the distributions observed compared with normal populations. The leukemic population contained an excess of individuals homozygous for haptoglobin type 1–1 and a deficiency of individuals homozygous for haptoglobin type 2–2. Data from similar clinical studies and a comparison of the incidence of haptoglobin genes and leukemia mortality suggest that the gene for haptoglobin protein type 2 confers resistance to leukemia on the holder to such an extent that the relative risk of leukemia among homozygous 1–1 as compared with subjects 2–2 is approximately fourfold. The observed dirferences in susceptibility may be related to the chemical action of haptoglobin on some leukemogenic agent.