Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?

BACKGROUND: Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment. METHODS: From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment. RESULTS: Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%). CONCLUSIONS: We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance.

ProMACE-cytaBOM versus MACOP-B in intermediate and high grade NHL. Preliminary results of a prospective randomized trial.

One hundred seventy-nine patients with intermediate or high-grade non-Hodgkin's lymphoma were randomized to receive either ProMACE-CytaBOM (P-C) or MACOP-B (M-B). At last follow-up 71 patients in the P-C arm and 78 in the M-B arm were assessable for response. Forty-one patients treated with P-C (58%) and 49 patients treated with M-B (63%) achieved a CR. Moreover 18 and 22 patients achieved PR with P-C and M-B, respectively. Twenty-five patients relapsed, 12 in the P-C arm and 13 in the M-B arm. Thirty-nine patients died, 32 from disease progression, 5 from treatment related causes, and 2 from other causes. No differences between the two treatment groups were observed as regard to relapse or death-rate. At 27 months the survival rate was of 71.9% for patients treated with P-C and 70.7% for those treated with M-B. At 2 years the RFD rate was 64% and 60% for patients in P-C and M-B arm, respectively. Patients treated with M-B experienced an high rate of methotrexate-related toxicity. ProMACE-CytaBOM and M-B seem provided with similar activity. However P-C seem less toxic and more manageable in an outpatient setting.

Morphological, phenotypic and karyotypic characterization of a novel natural-killer-cell target - evidence of involvement of MHC class-I molecules in NK cell recognition.

A new cell line from a neoplastic ascites was established. This strain, designated PAT-206, was characterized by plastic adherence and a high proliferative potential without any specific growth factor requirement. Karyotype analysis showed that the line was of human chromosomal constitution and aneuploid. Surface marker analysis showed that CD45, CD33 and CD15 were positive. In addition, the presence of human cytokeratins was detected by cytoplasmic immunofluorescence. Interestingly, the cell line did not express major hystocompatibility complex (MHC) class I and II, and was more sensitive than the 'classic' K562 cell line, to killing mediated by fresh uncultured peripheral blood lymphocytes. Following differentiation with interferon-gamma, the cell line expressed MHC class I antigens and resulted resistant to natural killing mediated lysis. This novel NK cell target seems to be suitable for further studies on NK cell specificities.

Response to STI571 in chronic myelomonocytic leukemia with platelet derived growth factor beta receptor involvement: a new case report.

Based on its ability to inhibit the tyrosine kinase activity of ABL, as well as the c-kit and the Platelet Derived Growth Factor Receptor tyrosine kinases, the spectrum of diseases that may respond to STI571 is increasing. A recently recognized subgroup of myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS) has a t(5;12)(q33;p13) with the activation of the gene for PDGFBR which encodes a receptor tyrosine kinase. Here, we present the case of a patient, with MPD/MDS, and eosinophilia, carrying a translocation t(5;12)(q33;p13) who achieved a complete remission following treatment with STI571, 400 mg daily. At the time of writing he still remains in complete remission with an excellent performance status. There is clearly a need for further studies of STI 571in MPD/MDS with chromosomal translocations involving PDGFBR to confirm this promising initial result.

[Immunohistochemical study on the presence of CEA in primary brain tumors. Preliminary note]. / Studio immunoistochimico sulla presenza del CEA nei tumori cerebrali primitivi. Nota preliminare.

The immuno peroxidase histochemical technique produced optic microscopic evidence of CEA (carcinoembryonic antigen) in 19 out of 42 (42.25%) brain tumours including 12 astrocytomas, 6 glioblastomas and 1 ependymoma. The possibility of identifying CEA in such tumours is extremely interesting in view of the fact that CEA is currently the antigen most commonly studied and utilised in various types of non-cerebral cancers.

Resistance to PGE2 inhibition of PWM-stimulated lymphocytes from neoplastic patients.

PGE2 treatment of mononuclear cells from patients with different types of neoplasias was unable to decrease either the number of plaque-forming cells or the expression of CD71 and CD25 in PWM-driven cultures. In contrast, in previous studies, PGE2 inhibited these parameters in cultured mononuclear cells from normal volunteers. Surgical treatment of cancer patients did not modify the lymphocyte sensitivity to PGE2 after 1 week, but at 2 and 6 months after therapeutical treatment, the inhibition values of the parameters studied were almost similar or very similar to those of normal lymphocytes. The reduction of PGE2 sensitivity in cancer patients was related to the increase of PGE2 levels and, probably, to a PGE2 receptor saturation. A restoration of PGE2-induced inhibition some months after therapy could be due to the decrease in PGE2 levels and to receptor unsaturation.

[Prognosis of colorectal tumors in patients with synchronous polyps]. / Prognosi dei tumori del colon-retto in soggetti con polipi sincroni.

A retrospective study was carried out in 110 patients who underwent colon resection for cancer of the colon-rectum. Polypoid formation reappeared in 10 (21.5%) patients in whom synchronous polyps were found around carcinoma during initial staging; during the follow-up polyps were only found in 3% of patients in whom synchronous polyps had not been documented. A similar ratio was found in the incidence of neoplastic recurrences which was greater (14%) in patients with synchronous polyps. This incidence was higher in cases with multiple polyps and/or polyps larger than 2 cm in size, and in relation to their histological type. The authors suggest that a more comprehensive operation, for example subtotal colectomy, should be performed in patients at greater risk to develop a second primary carcinoma, and/or that a particularly careful post-operative follow-up should be carried out in these patients.

Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease.

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow-up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin's disease, is needed.