Parameter perturbations in a post-treatment chronic myeloid leukemia model capture the essence of pre-diagnosis A-bomb survivor mysteries.

A model of post-diagnosis chronic myeloid leukemia (CML) dynamics across treatment cessations is applied here to pre-diagnosis scenarios of A-bomb survivors. The main result is that perturbing two parameters of a two-state simplification of this model captures the essence of two A-bomb survivor mysteries: (1) in those exposed to > 1 Sv in Hiroshima, four of six female onsets arose as a cluster in 1969-1974, well after 5-10-year latencies expected and observed in two of six female- and nine of ten male cases (about one background case was expected in this high-dose cohort); and (2) no Nagasaki adult cases exposed to > 0.2 Sv were observed though about nine were expected (~ 1.5 background + ~ 7.5 radiation-induced). Overall, it is concluded that: (1) whole-body radiation co-creates malignant and benign BCR-ABL clones; (2) benign clones are more likely to act as anti-CML vaccines in females than in males; (3) the Hong Kong flu of 1968 (and H3N2 seasonal flu thereafter) exhausted anti-CML immunity, thereby releasing radiation-induced clones latent in high-dose Hiroshima females; and (4) benign cells of 1-2 are CD4+ as human T-cell leukemia-lymphoma virus-1 endemic to Nagasaki but not Hiroshima expands numbers of such cells. The next goal is to see if these conclusions can be substantiated using banked A-bomb survivor blood samples.

Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population-Based Study.

BACKGROUND: To understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients. METHODS: We performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999-2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results-Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery. RESULTS: Of 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow-up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16-9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07-2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity-modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09-2.54). CONCLUSIONS: Our findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow-up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437-445, 2017. © 2016 Wiley Periodicals, Inc.

T-cell acute lymphoblastic leukaemia after liver transplantation: post-transplant lymphoproliferative disorder or coincidental de novo leukaemia?

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed.

[Health consequences in overexposed persons after the Chernobyl accident: basic resume and unsolved problems].

Data of researches of consequences for health after the Chernobyl accident in 1986 are generalized. Consequences for health of these groups and principles of the further supervision over them are estimated. The increasing of leukemia among the reasons attracts attention.

Role of radiation dose in the risk of secondary leukemia after a solid tumor in childhood treated between 1980 and 1999.

PURPOSE: The purpose of this study was to estimate the risk of secondary leukemia as a function of radiation dose, taking into account heterogeneous radiation dose distribution. METHODS AND MATERIALS: We analyzed a case-control study that investigated the risk of secondary leukemia and myelodysplasia after a solid tumor in childhood; it included 61 patients with leukemia matched with 196 controls. Complete clinical, chemotherapy, and radiotherapy histories were recorded for each patient in the study. Average radiation dose to each of seven bone marrow components for each patient was incorporated into the models, and corresponding risks were summed up. Conditional maximum likelihood methods were used to estimate risk parameters. RESULTS: Whatever the model, we failed to evidence a role for the radiation dose to active bone marrow in the risk of later leukemia, myelodysplasia, or myeloproliferative syndrome, when adjusting for epipodophyllotoxin and anthracycline doses. This result was confirmed when fitting models that included total dose of radiation delivered during radiotherapy, when fitting models taking into account dose per fraction, and when restricting the analysis to acute myeloid leukemia. CONCLUSIONS: In contrast to results found in similar studies that included children treated before the use of epipodophyllotoxins, this study failed to show a role for radiotherapy in the risk of secondary leukemia after childhood cancer in children treated between 1980 and 1999. This discrepancy was probably due to a competitive mechanism between these two carcinogens.

[Four cases of hematologic malignancy following radioactive iodine therapy for thyroid cancer].

Ionizing radiation including I(131) might produce chromosomal translocation, causing hematologic malignancy. The incidence of leukemia following radioactive iodine treatment for thyroid cancer has been reported to be approximately 0.1 to 2.0% in Western countries, whereas fewer cases have been reported in Korea. We hereby report four cases of secondary hematologic malignancy, who received iodine therapy for thyroid cancer after thyroidectomy: two cases of acute lymphoblastic leukemia with t(9;22)(q34;q11.2), a case of MDS with 5q deletion, and a case of MDS with normal karyotype. Three cases of hematologic malignancy have developed after cumulative dosage of less than 800 mCi. The treatment intervals in two cases were less than 12 months, and the other two cases had I(131) therapy only once. Assessment of causality using the Naranjo probability scale for adverse drug reactions showed that a 'possible' relationship existed between the use of I(131) and secondary hematologic malignancy in all of the four cases in this report.

Four Cases of Hematologic Malignancy Following Radioactive Iodine Therapy for Thyroid Cancer / 대한진단검사의학회지

Ionizing radiation including I131 might produce chromosomal translocation, causing hematologic malignancy. The incidence of leukemia following radioactive iodine treatment for thyroid cancer has been reported to be approximately 0.1 to 2.0% in Western countries, whereas fewer cases have been reported in Korea. We hereby report four cases of secondary hematologic malignancy, who received iodine therapy for thyroid cancer after thyroidectomy: two cases of acute lymphoblastic leukemia with t(9;22)(q34;q11.2), a case of MDS with 5q deletion, and a case of MDS with normal karyotype. Three cases of hematologic malignancy have developed after cumulative dosage of less than 800 mCi. The treatment intervals in two cases were less than 12 months, and the other two cases had I131 therapy only once. Assessment of causality using the Naranjo probability scale for adverse drug reactions showed that a 'possible' relationship existed between the use of I131 and secondary hematologic malignancy in all of the four cases in this report.

Leukemia following breast cancer: an international population-based study of 376,825 women.

PURPOSE: To quantify long-term temporal trends in the excess absolute risk (EAR) of secondary leukemia among breast cancer (BC) survivors, using multivariate analyses to evaluate the effects of subtype, age at BC diagnosis, attained age, and calendar year. PATIENTS AND METHODS: We identified 376,825 1-year survivors of BC within 4 nationwide, population-based cancer registries in Sweden, Denmark, Finland, and Norway (1943-2001). Estimates of EAR (per 100,000 person-years) were modeled using Poisson regression methods and cumulative risks calculated using a competing risk model. RESULTS: A total of 687 non-chronic lymphocytic leukemias (EAR = 9.05; 95% confidence interval (CI) = 7.5-10.7) was reported. Significantly elevated risks were observed for the first time for chronic myeloid leukemia (CML) (EAR = 2.06; 95% CI = 1.3-2.9) and acute lymphoblastic leukemia (ALL) (EAR = 0.62; 95% CI = 0.2-1.1), in addition to acute myeloid leukemia (AML) (EAR = 5.00; 95% CI = 3.9-6.2). Excesses of CML, ALL, AML and all leukemias combined persisted over 25 years after BC diagnosis. For all leukemias, EAR decreased with increasing calendar year (P = 0.04) of BC diagnosis. Risk for all leukemia and AML by calendar year of BC diagnosis depended on age at diagnosis. For women diagnosed with BC after 1985, the 10-year cumulative risk of leukemia for those diagnosed before and after age 50 was small, 0.10% and 0.14%, respectively. CONCLUSIONS: Although secondary leukemia is a rare event, BC survivors experience statistically significant excesses for at least 25 years after diagnosis, including CML and ALL. Decreasing leukemia risks in recent calendar years likely reflect changes in treatment.

Cutaneous nodes in a patient with advanced papillary carcinoma of the thyroid.

Cutaneous metastasis from thyroid carcinoma is infrequent. Leukemia as a second malignancy after treatment of thyroid cancer is also rare. We present a patient with a relapsed thyroid carcinoma treated with thyroid ablation with I 131 and loco-regional radiotherapy, who consulted by global worsening, weight lost, and multiple cutaneous nodes. Our patient is unusual in that she showed multisystem involvement at the time of hospital admission, and the specific skin lesions were the first sign of her acute monocytic leukemia.

Cutaneous nodes in a patient with advanced papillary carcinoma of the thyroid

Cutaneous metastasis from thyroid carcinoma is infrequent. Leukemia as a second malignancy after treatment of thyroid cancer is also rare. We present a patient with a relapsed thyroid carcinoma treated with thyroid ablation with I 131 and loco-regional radiotherapy, who consulted by global worsening, weight lost, and multiple cutaneous nodes. Our patient is unusual in that she showed multisystem involvement at the time of hospital admission, and the specific skin lesions were the first sign of her acute monocytic leukemia (AU)

[The risks of out of area missions: depleted uranium]. / I rischi delle missioni fuori area: l'uranio impoverito.

Depleted uranium (DU), a waste product of uranium enrichment, has several civilian and military applications. It was used as armor-piercing ammunition in international conflicts and was claimed to contribute to health problems, known as the Gulf War Syndrome and recently as the Balkan Syndrome. Leukaemia/Limphoma cases among UN soldiers in the Balkans have been related hypothetically to exposure to DU. The investigations published in the scientific literature give no support for this hypothesis. However future follow-up is necessary for evaluation of long-term risk.

Aleukaemic leukaemia cutis as an initial manifestation of myeloid/NK cell precursor acute leukaemia.

Aleukaemic leukaemia cutis is a rare condition characterized by infiltration of leukaemic cells into the skin before they appear in the peripheral blood. We report a case of an aleukaemic leukaemia cutis, which had a history of exposure to atomic bomb radiation. A 57-year-old Japanese woman initially presented with a 20-week history of multiple red papules and plaques mainly over the trunk. Histological examination revealed the infiltration of atypical monocytic cells in the dermis, but no leukaemic cells were detected in the peripheral blood. Twenty-three weeks after the appearance of the eruption, leukaemic cells were detected in the peripheral blood for the first time. The results of immunohistochemistry of the skin biopsy specimen and flow cytometry of the peripheral blood indicated the rare phenotype of myeloid/NK cell precursor acute leukaemia. This is the first case report of myeloid/NK cell precursor acute leukaemia presenting as aleukaemic leukaemia cutis in the English literature, and awareness of this clinical presentation may be important to reach the correct diagnosis.

Chronic myeloid leukemia in a man with papillary carcinoma of the thyroid treated with radioactive iodine.

Leukemia as a second malignancy after treatment of thyroid cancer is rare. Most cases reported in the literature have occurred after cumulative doses higher than 800 mCi and it is most commonly acute leukemias. We report a case of chronic myeloid leukemia (CML) occurring in a 40-year-old man 14 years after treatment of papillary thyroid carcinoma. Our patient had the longest interval between the diagnosis of CML and administration of 131I.

Mature B-cell leukemias with more than 55% prolymphocytes: report of 2 cases with Burkitt lymphoma-type chromosomal translocations involving c-myc.

CONTEXT: The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified Burkitt lymphoma-type chromosomal translocations involving 8q24. OBJECTIVE: To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes. RESULTS: In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. Fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22). CONCLUSION: These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.

[The characteristics of the pre- and leukemic stages of chronic myeloproliferative diseases in persons suffering as a result of the Chernobyl catastrophe]. / Kharakteristika pre- i leikemicheskoi stadii khronicheskikh mieloproliferativnykh zabolevanii u lits, postradavshikh vsledstvie chernobyl'skoi katastrofy.

Clinical, morphological and cytogenetic investigations were done in those patients with leukocytosis having become victims of the Chernobyl catastrophe. Of these (n = 10), six patients demonstrated chromosomal abnormalities. In the study made at a later date in six patients with cytogenetic abnormalities, five patients were found to have chronic myeloproliferative disorders, with four cases presenting with chronic myeloid leukemia and one patient having osteomyelofibrosis.

[The clinical course and histological characteristics of medullary hematopoiesis in acute leukemia in those who worked in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station]. / Klinichnyi perebih ta histolohichni osoblyvosti kistkovomozkovoho krovotvorennia pry hostromu leikozi u likvidatoriv naslidkiv avariï na ChAES.

The course is analyzed of myeloblastic leukemia in twelve participants in the elimination of the aftermath of the Chernobyl Atomic Power Plant breakdown. The iliac trepanobiopsies bone-marrow hemopoiesis is studied. A gross depression of normal hemopoiesis has been revealed together with a fibrous transformation of the bone marrow, which fact suggests a profound damage to the hemopoietic micro-surroundings, being a cause of ineffective hemopoiesis, of grave course of the illness, and of failure to respond to cytostatic therapy.