Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia

The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase- type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S- 2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u- PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.     

Factor V Leiden and allogeneic bone marrow transplantation: chimerism as a confounding factor in genetic test interpretation

Factor V Leiden is one of the most common genetic conditions predisposing to venous thrombosis. Diagnosis is currently made by plasma activity assay for activated protein C (APC) resistance or polymerase chain reaction (PCR)-based DNA assay. The occurrence of factor V Leiden is reported in a patient affected by acute myeloid leukaemia submitted to allogeneic bone marrow transplantation from an HLA identical sister. The donor was not affected by the factor V mutation. The patient did not develop thrombosis during induction and consolidation chemotherapy and the post-transplantation course was not complicated by thrombosis or veno-occlusive disease. At engraftment, PCR analysis showed the disappearance of factor V Leiden. Genetic tests on DNA after allogeneic marrow transplantation should be carefully interpreted as a result of donor chimerism.     

Cyclooxygenase-2 expression in borderline ovarian tumors

OBJECTIVES: The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors. METHODS: Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive. RESULTS: Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22). CONCLUSIONS: COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis.     

Successful multimodal treatment of a breast cancer patient with a recurrence invading the chest wall

We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life.     

Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.     

Acute myeloid leukemia after iodine-131 treatment for thyroid disorders

 Leukemia has rarely been reported as a late complication of ¹³¹I therapy, occurring mostly after cumulative doses of 800 mCi. We observed two cases of acute myeloid leukemia (AML) after ¹³¹I therapy for hyperthyroidism and thyroid carcinoma, respectively. The first patient was a 45-year-old woman treated with a single dose of 27 mCi ¹³¹I for hyperthyroidism. She developed AML (FAB M2) 14 months after receiving ¹³¹I; the second patient was a 44-year-old man affected by refractory thyroid carcinoma who received a total dose of 1 Ci ¹³¹I plus radiotherapy and developed AML (FAB M6) 8 years after the first exposure to ¹³¹I. Although it is a very rare event, the occurrence of leukemia after ¹³¹I treatment should be kept in mind, considering the widespread use of ¹³¹I, particularly in the treatment of hyperthyroidism, and the unfavorable outcome of secondary leukemia. Received: 2 December 1997 / Accepted: 3 March 1998     

Feasibility and outcome of interval debulking surgery (IDS) after carboplatin-paclitaxel-bevacizumab (CPB): A subgroup analysis of the MITO-16A-MaNGO OV2A phase 4 trial

Background

Few data are available on the outcome of surgery after a bevacizumab-containing regimen. The MITO 16A- MaNGO OV2A phase 4 trial evaluates the outcomes of first-line CPB in a clinical-practice-like setting. Here we present the results of the subgroup of patients undergoing IDS after neoadjuvant treatment or suboptimal primary surgery.

Sudden death by sleep apnea syndrome associated with myxedema. A case report and a review of the literature

The case is presented of a 48-year old, slightly overweight, brachymorphic male affected by undiagnosed myxedema, admitted for nocturnal dyspnea present for several years but worsened in the last few weeks. At the age of 19, a paranoid schizophrenia diagnosis was indicated leading to repeated admissions to psychiatric hospitals and continued pharmacological therapy. His sensorium was lucid albeit with a slight psycho-motor slowing down; pharyngeal edema and macroglossia were also apparent, blood O2 saturation was 97%. After the first emergency exams, a hypothyroid condition associated with multinodular goiter and tracheal dislocation was found. Administration of triiodothyronine p.o. and hydrocortisone i.v. was thus initiated. In the doubt of sleep apnea syndrome (SAS) occurrence, pulse oximetry was performed, but after 7 hours, the patient suddenly deceased. Data showed waves of deep O2 desaturation secondary to periods of prolonged apnea. A literature review shows that such a case has never been reported. A posteriori analysis of the patient's clinical management indicates that the obstructive form of SAS, associated with myxedema is a condition which needs to be promptly diagnosed; due to the possible seriousness of its functional evolution, the need for intensive or sub-intensive therapy, with continuous nasal airway positive pressure or with oro-tracheal intubation and assisted ventilation, should be carefully taken into consideration; continuous cardiac monitoring should also be carried out, given the risk for acute coronary complications and ventricular arrhythmias in the early phases of substitutive therapy with thyroid hormone.     

Neoadjuvant therapy changes the lymphocyte composition of tumor-draining lymph nodes in cervical carcinoma

BACKGROUND: The objective of the current study was to illustrate the influence of neoadjuvant therapy on the local immune response in patients with cervical carcinoma. METHODS: Uninvolved tumor-draining lymph nodes (TDLN) (n=158 lymph nodes), including internal, external, and common iliac lymph nodes as well as obturator, presacral, and aortic lymph nodes from 15 nontreated (NT) patients, 4 chemotherapy (CT)-treated patients, and 19 chemoradiation (CR)-treated patients, were analyzed for lymphocyte subset distribution and for the proliferative response of T cells to polyclonal activation and interferon-gamma (IFN-gamma) production. Lymphocyte subsets in peripheral blood also were assessed. RESULTS: TDLNs from CR-treated patients contained higher proportions of CD8+ cells and natural killer cells than NT and CT-treated patients (P values ranged from <0.05 to <0.01). TDLNs from CR-treated patients were enriched in activated-type CD4+ cells (HLA-DR+, CD134+, CD62L-, and CD25+ at an intermediate expression level; P values ranged from <0.05 to <0.01) and activated-type CD8+ cells (CD62L-, P<0.001) compared with NT patients. Concomitantly, there was a reduction in the proportion of na?ve-type CD4+ and CD8+ cells (CD45RA+/CD62L+) (P<0.01 and <0.05, respectively). CR treatment increased the proportion of both CD4+ and CD8+ cells prone to produce IFN-gamma. All TDLNs contained suppressive CD4+ T regulatory (Treg) cells (CD25+ and CD152+ at a high expression level) whose frequency and suppressive activity was not influenced by the treatment. Therapy-induced changes in TDLN were mirrored only in part by respective alterations in peripheral blood. CONCLUSIONS: To our knowledge, the current study is the first to show that neoadjuvant therapy produces an enhancing effect on the immune competency of TDLNs from patients with cervical carcinoma.