[Low-dose accelerated hyperfractionated radiotherapy for local control of chemoresistant Hodgkin's disease (a prospective randomized trial)].

The results are evaluated of the combined treatment of 154 patients with relapsed refractory Hodgkin's disease, which was conducted using standard dosage of conventional chemotherapy. Out of those, 117 with residual lesions were randomized to receive either focal radiotherapy (20-24 Gy) in accelerated hyperfractionation (1.3-1.5 Gy, twice a day, at 5-hr interval) or 38-40 Gy in standard fractionation. Local control persisted in 85-97% of irradiated sites (median follow-up of 24 months), irrespective of irradiation technique. TTD being lowered down to 20-24 Gy due to use of accelerated hyperfractionation, the frequency of late-onset radiation injuries of paramediastinal lung tissue was lower than in standard treatment, with a subsequently lower fraction of patients with stage II fibrosis.

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

[New developments in understanding the compensatory hematological reactions and their outcomes in local fractionated therapeutic gamma irradiation]. / Novoe v ponimanii kompensatornykh gematologicheskikh reaktsii i ikh iskhodov pri lokal'nom fraktsionirovannom terapevticheskom gamma-obluchenii.

We have carried out a study of the bone marrow status in both irradiated and non-irradiated zones of 56 patients with stage I-II Hodgkin's disease in complete 9-12 (33 patients, group 1) and 18-23 (23 patients, group 2) year remission after therapeutic irradiation of the supradiaphragmatic lymphatic collectors at a dose of 40 Gy with irradiation of the spleen (33 patients) or splenectomy (23 patients). The total count of myelokaryocytes, myelogram, a relative and absolute content of lymphoid cells, immature granulocytes and elements of erythroid series were calculated in the aspirates from the exposed to radiotherapy sternum and non-irradiated upper portion of the ileum. The number of granulocyte-macrophage (CFU-GM) and stromal (CFU-F) precursor cells were defined using in vitro culture technique. There was a complete annihilation of the bone marrow in the irradiated zones, when the dose exceeded 35 Gy in 3-4 weeks. The concentration of myelokaryocytes, immature granulocytes, erythronormoblasts, CFU-GM, CFU-F in non-exposed bone marrow were significantly lower in all patients of group 2 than in normal subjects and in group 1 patients. Absolute lymphoid count in patients with 18-23 year remission was found to be normal but was considerably reduced in comparison to patients of group 1. These changes may be the result of the previous hyperactivity of the non-irradiated bone marrow which could be a cause of stem cell compartment depletion. The differential calculation of compact and diffuse subpopulations of CFU-F revealed a significant reduction of compact colony-forming CFU-F in both irradiated and unexposed bone marrow. Almost all the stromal precursor cells from irradiated zone formed diffuse colonies in cultures. These results confirm experimental data concerning greater radiosensitivity and proliferative potential of CFU-F, forming compact colonies versus diffuse colony-forming CFU-F. Aplasia of the irradiated bone marrow and hypoplasia of the non-irradiated bone marrow 18-23 years after radiotherapy completion coexisted with normal circulating CFU-GM and granulocyte blood count suggesting a compensatory mechanism involving a mitotic amplification between the progenitor cell and the final differentiated cell.

[The bone marrow in Hodgkin's disease following radiotherapy and splenectomy]. / Kostnyi mozg pri limfogranulematoze posle luchevoi terapii i splenéktomii.

A study was made of the bone marrow status in unirradiated zones of 33 patients with stage I-II Hodgkin's disease in complete 9-12 year remission after therapeutic irradiation of the lymphatic collectors of the upper part of the trunk in combination with irradiation of the spleen (16 patients) or splenectomy (17 patients). The total count of myelokaryocytes, myelogram, a relative and absolute content of lymphoid cells, immature granulocytes and elements of the erythroid series were defined in the punctates of the upper portion of the ilium. T- and B-lymphocyte count, the number of granulocytomacrophage (CFU-C) and stromal (CFU-F) precursor cells were defined using morphocytochemical and immunological methods. At that time an increase in the relative and absolute content of C- and B-lymphocytes was noted. The T-cell count and the total number of myelokaryocytes, on the one hand, and the content of immature granulocytes and erythronormoblasts, on the other hand, showed correlation of various degree which was particularly noticeable in the group of unoperated patients. The total number of myelokaryocytes in 1 microliter of the bone marrow of the patients after splenectomy, on an average, significantly exceeded that in the group of patients with the irradiated spleen. These changes were considered to be a result of the rearrangement of T-differentiating lymphocytes with their raised accumulation in the bone marrow after irradiation of a considerable volume of the lymphoid tissue and spleen or after splenectomy.

[Role of splenectomy in impairing lymphocyte elimination in patients with lymphogranulomatosis]. / Rol' splenéktomi v narushenii éliminatsii limfotsitov u bol'nykh immunogranuletmatozom.

The study group included 113 patients in a continuing 1 to 10 year-long complete clinical-hematological remission from Hodgkin's disease. 43 of them had prior splenectomy. The latter revealed a higher level of lymphocytes (chiefly 0-cells) and a diminished response of mononuclear blood cells to PHA as compared to the other patients and healthy controls. Also, they had more lymphocytes which became capable of E-rosette formation following a short-term incubation at 37 degrees C (lymphocyte reactivation by means of surface modification). The negative correlation between the reactivated T-cells level and mononuclear cell response to PHA suggested a functional blocking of T-cells involving damage to membranes. The absence of reactivated T-lymphocytes in nonsplenectomized patients was regarded as circumstantial evidence for the role played by the spleen in withdrawing faulty lymphocytes from peripheral blood.