Testicular Function after Combination Chemotherapy for Hodgkin's Disease

Fertility was estimated by sperm counts and hormone assays in 8 patients treated for Hodgkin's disease with at least 6 courses of combination chemotherapy. This consisted of an alkylator (mechloretamine or cyclophosphamide), a vinca alkaloid (vinblastine or vincristine), procarbazine and prednisone. Azoospermia was found in 7 of the 8 patients on examination 12–29 months after termination of chemotherapy. In 1 patient semen quality improved gradually, and a sperm count of 5 mill/ml was found at 21 months. Serum FSH levels were increased in all but 1 patient who was, nevertheless, azoospermic. The levels of testosterone and LH were generally within normal limits. Thus, the germinal tissue is seriously damaged by this type of chemotherapy. The resulting infertility seems to be complete and of long duration. Partial recovery of spermatogenesis may, however, sometimes take place after prolonged unsustained remission.     

Testicular Function after Radiotherapy to Inverted ‘Y’ Field for Malignant Lymphoma

Testicular function was estimated by sperm counts, hormone assays and recording of reported conceptions in 9 patients irradiated for malignant lymphoma. The treatment had been an inverted ‘Y’ field including the inguinal regions with, in addition, a mantle field in 8 patients. Azoospermia or severe oligozoospermia was found in all but 1 patient, and the FSH levels were uniformly elevated. Testosterone and LH were within normal limits except in 2 patients with slightly subnormal testosterone levels. 7 of the patients were married to women of fertile age, and in 3 cases the wife became pregnant and gave birth to a healthy child. The time lapses from irradiation to conception were 18, 40 and 57 months. 2 of these patients had severe oligozoospermia on examination 2 and 4 months respectively from conception. Thus fertility may possibly be underestimated by sperm counting and hormone assays after this type of radiotherapy.     

The course of anxiety and depression during the first year after allogeneic or autologous stem cell transplantation

Psychological distress is frequently reported in transplant survivors. We prospectively assessed anxiety and depression before transplant, in the isolation period and during a follow-up period of 1 year. The Hospital Anxiety and Depression Scale (HADS) was administered to 131 cancer patients treated with high-dose chemotherapy followed by allogeneic (SCT) or autologous (ASCT) stem cell transplantation, and a concurrent group of 123 lymphoma patients receiving standard chemotherapy (CT) who served as a reference group. Relatively low levels of anxiety and depression were found. The level of anxiety slightly declined from baseline during follow-up (mean scores SCT: from 5.3 to 3.6, CT: from 6.0 to 4.2) or remained fairly stable (ASCT: from 5.4 to 4.8). The level of depression peaked when the transplant patients were in protective isolation or shortly thereafter (SCT: 6.1, ASCT: 6.4), but stabilized at baseline levels after 4 months. The highest level of depression in the CT group was reported 4 months after start of chemotherapy (3.4). Elevated levels of anxiety and depression at baseline predicted more anxiety and depression at the later assessments (P values < 0.0001). The ASCT group had higher levels of anxiety after 1 year (mean 4.8) than those found in the other two groups (SCT: 3.6, CT: 4.2), although they were not statistically significant. This study revealed lower than expected levels of anxiety and depression after intensive chemotherapy followed by SCT or ASCT. There was a decline in psychological distress during the 1-year follow-up period.     

Improvement of prognosis in refractory and relapsed acute promyelocytic leukemia over recent years: the role of all-trans retinoic acid therapy

 With the aim of determining the ability of all-trans retinoic acid (ATRA) to improve prognosis in refractory and relapsed acute promyelocytic leukemia (APL), the data of 45 patients resistant to previous conventional chemotherapy or in first relapse were retrospectively reviewed. Thirty-seven patients presented with typical M3, five with variant form (M3v), and three with intermediate form. Seven patients died before any chemotherapy could be given. Thirty-five patients received one course of chemotherapy combining anthracyclines and cytarabine without (n=22) or with ATRA (n=13), according to different protocols. One elderly patient received only ATRA, and two patients received only low-dose cytarabine. Nine patients died within 4 weeks of relapse. A complete remission (CR) was achieved in 29 of the 38 patients retreated after first relapse or primary failure (76.3%, 95% CI: 60–89%). Among relapsed patients, four of five patients who had initially received ATRA therapy achieved a second CR when retreated by ATRA. The median second disease-free survival (DFS) was 23.3 months. Overall median survival was 7.8 months, with a 5-year survival rate of 29% (95% CI: 14–44%). Parameters found to be associated with decreased second CR rate were presence of hemorrhages and hemostatic disorder, and high levels of GGT at the time of relapse. Factors associated with short survival were WHO performance status >1, high serum LDH levels, and coagulopathy at time of relapse. Use of ATRA at time of relapse (n=14) was significantly associated with higher CR rates (p=0.008), longer DFS (median not reached versus 7.9 months;p=0.05), and longer survival after first relapse (median 32.3 months versus 4.4 months;p=0.003). In the multivariate analysis, the only factor predictive of poor prognosis for overall survival was the absence of ATRA therapy at relapse. We conclude that ATRA is effective in the treatment of relapsed or refractory APL and appears superior to chemotherapy alone. Received: 13 June 1997 / Accepted: 8 September 1997     

All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases.

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course ("4 + 7" course), then three "2 + 5" DNR + Ara C courses and maintenance chemotheapy. However, the "4 + 7" course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the "4 + 7" course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the "4 + 7" course. Four patients did not receive this course but received the subsequent "2 + 5" courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Primary cardiac lymphoma: diagnosis and treatment. Report of 6 cases and review of the literature

Primary cardiac lymphoma (PCL) is the rarest primary cardiac tumour and carries a poor prognosis. Early diagnosis, often difficult, to introduce appropriate treatment as soon as possible, seems to have a positive impact on prognosis. The authors report their experience of 6 patients with PCL. None of the patients had immune depression. The presentations were tamponade (N= 2), right heart failure (N= 1), general ill health (N= 3). A PCL was suspected on echocardiography and thoracic CT scan showing tumour invading the right heart chambers in all cases. The diagnosis of PCL was confirmed by surgical biopsy in 5 patients and by endomyocardial biopsy in 1 patient. A diffuse large cell type B lymphoma was found in 5 patients and an anaplastic lymphoma in 1 patient. One patient died of right heart failure 4 days after diagnosis and before starting chemotherapy. All the other patients received chemotherapy. Two patients died during their first course. The other three patients had several courses of chemotherapy: there are two survivors 17, 5 months later and one patient died 62 months after diagnosis. The diagnosis of PCL should be suspected in patients with a cardiac tumour associated or not with pericardial effusion. Early, appropriate chemotherapy seems to have a positive impact on the prognosis, justifying aggressive approaches to obtain a rapid histological diagnosis.     

Hyperuricemia and arthralgia during pyrazinamide treatment]

We studied 51 pulmonary tuberculosis patients who were initially treated with pyrazinamide (PZA) at our hospital between April 1996 and December 1997. PZA dosage was less than 1.5 g per day, and the chemotherapy course lasted 2 months. Uric acid levels of higher than 8 mg/dl were observed in 44 patients (86%). Arthralgia was observed in 9 patients. Acute gout was observed in only 1 patient who had hyperuricemia prior to PZA treatment and a predisposition for gout. The other 8 patients with arthralgia had symptoms in the shoulders and knees, but no gouty pain. Arthralgia was not related to serum uric acid level and disappeared after PZA treatment was stopped. We concluded that PZA can be used for up to 2 months without the combined administration of allopurinol or benzbromarone even if hyperuricemia or arthralgia develops.     

Effects of combination chemotherapy and highly active antiretroviral therapy on immune parameters in HIV-1 associated lymphoma

OBJECTIVE: To measure the effects of combined chemotherapy and highly active antiretroviral therapy (HAART) on immune cell counts and plasma HIV-1 RNA loads in patients with AIDS-related lymphoma (ARL) to determine the implications for opportunistic infection prophylaxis and medium-term immune function. DESIGN AND METHODS: Peripheral blood total lymphocyte count, CD4 T-cell count, CD8 T-cell count, CD19 B-cell count, CD16/CD56 natural killer cell count and plasma HIV-1 RNA load were prospectively measured at ARL diagnosis, at 1 and 3 months during and 1, 3 and 6 months after chemotherapy in twenty patients receiving HAART. RESULTS: Significant declines in T-helper cell (CD4) count, natural killer cell (CD16/CD56) and B lymphocyte count (CD19 cells) occurred during the first 3 months of chemotherapy. There was no significant alteration in the T-cytotoxic cell (CD8) count, CD4 percentage or HIV-1 RNA load during the study period. The T-helper cell and natural killer cell counts recovered to pre-treatment levels within 1 month of finishing chemotherapy. The recovery of B-cells was slower with pre-treatment levels only being achieved after 3 months. The recovery of CD4 T-cell count following completion of chemotherapy was more rapid than described for ARL patients who were not receiving concomitant HAART. CONCLUSIONS: By combining chemotherapy with HAART, immune function is better maintained in the medium term. The CD4 T-cell count falls by 50% during chemotherapy and this will help to identify patients who require opportunistic infection prophylaxis during chemotherapy.     

Acute promyelocytic leukemia: All-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA. Am. J. Hematol. 60:87–93, 1999. © 1999 Wiley-Liss, Inc.     

Subsequent resection of locally advanced pancreatic carcinoma after chemoradiotherapy

OBJECTIVES: The aim of this study was to evaluate the possibility of subsequent resection of locally advanced pancreatic adenocarcinoma after chemotherapy and external-beam radiotherapy. PATIENTS AND METHODS: Between January 1996 and January 2001, 33 consecutive patients (18 males and 15 women, mean age 63 years) with locally advanced PA were treated with chemotherapy and concurrent external-beam radiotherapy. Radiotherapy delivered 45-50.4 Gy, in a classical manner (N=27) or on a split-course (N=6). Chemotherapy was made of 5FU by continuous infusion for all patients during 5 weeks and cisplatin at the 1st and 5th weeks (N=22). Tumor resectability was reassessed at the end of the chemoradiotherapy; surgical resection of tumour was attempted in patients whose tumor demonstrated reduction in size, and supplementary radiotherapy of 10 to 15 Gy was delivered to the others. RESULTS: Thirty-nine percent of patients experienced grade 3 acute toxicity. WHO criteria response to chemoradiotherapy four weeks after the end of treatment were: 4 partial responders (12%), 6 minor responders (18%), 14 stable disease (42%), 9 progression (28%). Ten patients underwent exploratory laparotomy, in one case vascular encasement did not allow for tumor resection, and in another patient, there was peritoneal carcinomatosis. In the 8 remaining patients, surgical (R0) resection was possible. In one patient histological examination showed fibrosis with no residual tumour. After a median follow-up period of 40 months, median survival was 16 months (66% and 37% of survival at 1 and 2 years respectively). In operated and non-operated patients, survival rates at 24 months were 73% and 12.5% respectively. At 1 year, 80% of the patients treated with radiochemotherapy developed recurrence, metastatic recurrence in 88%. Initial laparotomy, split course radiotherapy were poor outcome factors whereas chemotherapy appears to be a favorable outcome factor. CONCLUSION: Subsequent resection of locally advanced pancreatic adenocarcinoma is possible after chemoradiotherapy allowing for a prolonged survival in some patients.     

Delayed hepatitis B virus reactivation after cessation of preemptive lamivudine in lymphoma patients treated with rituximab plus CHOP

Preemptive lamivudine in lymphoma patients undergoing intensive chemotherapy can effectively prevent chemotherapy-related HBV reactivation. Nevertheless, the safety profile after withdrawal of lamivudine and the impact of rituximab-containing chemotherapy on HBV reactivation has not been defined. To illustrate the necessity of prolonged surveillance after cessation of preemptive lamivudine in lymphoma patients treated with rituximab and chemotherapy, four patients with B-cell NHL carrying HBV received rituximab plus CHOP. Preemptive lamivudine therapy was administered 1 week before chemotherapy until 4 weeks after completion of chemotherapy. Serial serum alanine aminotransferase (ALT), total bilirubin, and HBV-DNA levels were prospectively monitored in three patients. The fourth patient was closely monitored for ALT. The HBV DNA was checked after development of clinical overt hepatitis. The peripheral blood CD20⁺ B-lymphocyte counts were analyzed periodically in two patients. All of the three patients studied prospectively had virological relapses with surgence of HBV DNA 6–8 months after completion of rituximab-plus-CHOP (R+CHOP) therapy. Two of the three patients had biochemical relapses and one of them developed severe hepatitis. Sequencing for HBV polymerase gene in these patients failed to show evident emergence of lamivudine-resistant mutations. The fourth patient developed a hepatitis flare-up 6 months after completion of chemotherapy. The CD20⁺ lymphocytes were totally depleted when HBV DNA started to increase. Delayed HBV reactivation can occur in lymphoma patients receiving R+CHOP after withdrawal of preemptive lamivudine. More protracted lamivudine therapy may be an alternative to close monitoring following chemotherapy, and further studies are needed to define optimal duration of lamivudine therapy.     

Interferon and ribavirin treatment results of patients with HBV-HCV co-infection cured of childhood malignancies.

OBJECTIVES: We aimed to investigate the virological and clinical characteristics and the results of combination therapy in six oncology patients with hepatitis B virus (HBV)-hepatitis C virus (HCV) co-infection. METHOD: Six patients (five male and one female; age range 8-14 years), diagnosed with HBV-HCV infections during follow-up at the oncology outpatient clinic during 2000-2001 were included in the study. They had received an average of 25.8 units of blood by transfusion per patient during their treatment for malignancies. Positive serological HBV indicators were determined 20-40 months after the end of chemotherapy. HCV RNA positivity was determined together with HBV at an average of 3.3 months after hepatitis B infection. Patients received interferon-alpha-2b and ribavirin for 12 months. RESULTS: Both HBV DNA and HCV RNA became negative, and anti-HBe became positive in one patient. One patient had decreased HBV DNA levels and negative HCV RNA and HBeAg, but HBeAg became positive again at 18-months following treatment. Another patient had decreased serum HBV DNA and HCV RNA levels with normal ALT levels at the end of treatment; however, two months after therapy was ceased these values returned to pretreatment levels. CONCLUSION: We observed that combined treatment is effective in HBV-HCV infection. The effectiveness of combined treatment should be researched with larger groups of co-infected patients.     

Immunoreactive plasma inhibin levels in men after polyvalent chemotherapy of germinal cell cancer.

In vitro studies have shown that the Sertoli cell is the primary source of inhibin in the male. We measured immunoreactive inhibin with a new two-site immunoenzymatic assay in the plasma of 92 men: 40 normal men, 7 patients with germinal cell cancer after unilateral orchidectomy and 45 patients with the same disease following unilateral orchidectomy and subsequent chemotherapy based on cisplatin. Normal men had inhibin levels of 1.77 +/- 0.09 U/l x 10(-3) (mean +/- SEM). Seven patients after unilateral orchidectomy had inhibin concentrations within the lower normal range (1.23 +/- 0.22 U/l x 10(-3)). Forty-five patients were investigated in a cross-sectional study up to 102 months after completion of chemotherapy. Inhibin levels were within the normal range in 25 patients (1.76 +/- 0.14 U/l x 10(-3)); 18 patients had significantly lower inhibin levels (0.48 +/- 0.05 U/l x 10(-3), p less than 0.005) when compared to patients after unilateral orchidectomy. Two patients had elevated inhibin levels (4.4 and 5.6 U/l x 10(-3)). The proportion of patients with normal and subnormal inhibin was not dependent on the time that elapsed after completion of chemotherapy or on the chemotherapy combination. There was no correlation between immunoreactive plasma inhibin and LH, FSH, testosterone or sperm count. The decrease in inhibin concentrations after chemotherapy may indicate long-term damage to Sertoli cells in some of the patients.     

Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants

We studied the efficacy and safety of humanized CAR-T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B-ALL). Twenty-three patients with R/R B-ALL were pretreated with intensive chemotherapy (fludarabine combined with medium-dose cytarabine) 12 days before CAR-T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release syndrome (CRS) were monitored. Each of the 23 patients received a dose of 1·0 × 10⁶ cells/kg CAR-T cell infusion on day 0. After 14 days, 19 patients (82·61%) achieved complete response (CR) or CR with incomplete count recovery. No survival benefit was achieved with consolidative haematopoietic stem-cell transplantation (HSCT), with a median follow-up of 14·0 months (range, 1·5–21·0 months). The notable AEs were grade 1–2 CRS in 18 patients, while the other five patients were grade 3 CRS. No patients died of CRS. Only one patient died of respiratory failure due to cytomegalovirus infection 24 days after infusion. The proportion of leukaemic cells in bone marrow on infusion day and the peaks of IL-6, TNF-α and IL-8 levels were correlated with CRS levels. A lower disease burden was achieved by intensive lymphodepleting chemotherapy, and the subsequent CAR-T therapy had a high response and manageable toxicity. Trial registration: The patients were enrolled in a clinical trial of ChiCTR-ONN-16009862, and ChiCTR1800019622.     

Gynecomastia after chemotherapy for lymphoma

Although development of gynecomastia in a patient with cancer may indicate persistence or regrowth of a tumor, we studied three patients with lymphoma in whom development of gynecomastia during or after chemotherapy did not portend a poor outcome. In all patients, serum testosterone levels were normal, serum luteinizing hormone (LH) levels were high-normal or elevated, and serum follicle-stimulating hormone (FSH) levels were clearly elevated. The serum estradiol level of one patient was elevated at the onset of gynecomastia, but it fell to normal as the gynecomastia resolved spontaneously over a three-month period during which the patient received no chemotherapy. In a second patient, gynecomastia resolved over a period of eight months while the patient continued on maintenance chemotherapy, and he remains clinically well in remission 21/2 years after onset of gynecomastia. In the third patient, gynecomastia developed while the patient was in complete remission and off of all therapy, and it remained unchanged for the duration of a 21/2-year remission without therapy. Gynecomastia after chemotherapy for lymphoma is not an ominous prognostic sign and does not necessarily indicate the need for alteration of the treatment regimen.     

A prospective controlled study of the impact of hyperthyroidism on reproductive function in males

The aim of this prospective controlled study was to ascertain the effect of hyperthyroidism on sperm quality and composition. We studied 23 thyrotoxic male patients, aged 43.8 +/- 2.4 yr (mean +/- SEM), and 15 healthy male controls of approximately the same age (42.2 +/- 2.2 yr). Two semen analyses at intervals of 2-3 wk were obtained before and about 5 months after euthyroidism was achieved either by methimazole alone (14 patients) or (131)I plus methimazole (9 patients). Total fructose, zinc (Zn), and magnesium (Mg) were also measured in seminal plasma in 16 patients, because 7 had semen volume less than 2 ml. In the control group semen analysis was performed only once. Mean (+/-SEM) semen volume was within normal range both in patients (3.3 +/- 0.2 ml) and controls (3.5 +/- 0.4 ml; P = NS). Mean sperm density was lower in patients, although the difference compared with controls did not reach statistical significance (35.7 +/- 5.3 vs. 51.5 +/- 6.1 x 10(6)/ml; P = 0.062). The same was found with sperm morphology (68 +/- 7% vs. 78 +/- 8%; P = NS). Finally, mean motility was lower in thyrotoxic males than in controls (28 +/- 8% vs. 57 +/- 7%; P < 0.01). After treatment, sperm density and motility improved [35.7 +/- 5.3 vs. 43.3 +/- 6.5 x 10(6)/ml (P = NS) and 28 +/- 8% vs. 45 +/- 7% (P < 0.05), respectively], but sperm morphology did not change (68 +/- 7% vs. 70 +/- 6%; P = NS). Mean values for fructose, Zn, and Mg did not differ between controls and patients either before or after achievement of euthyroidism [9.2 +/- 0.7, 3.0 +/- 0.5, and 4.2 +/- 0.7 nmol/liter vs. 8.6 +/- 0.9, 3.0 +/- 0.5, and 4.7 +/- 0.8 nmol/liter (patients before) and 9.1 +/- 0.7, 3.1 +/- 0.6, and 4.5 +/- 0.9 nmol/liter (patients after treatment) for fructose, Zn, and Mg, respectively]. Moreover, according to the treatment given, no statistically significant differences were found before or after treatment. Finally, seminal plasma fructose, Zn, and Mg levels did not correlate with sperm parameters or with pretreatment thyroid hormone levels. In conclusion, the results of our study indicate that male patients with hyperthyroidism have abnormalities in seminal parameters, mainly sperm motility. These abnormalities improve or normalize when the patients become euthyroid. Restoration of sperm parameters was independent of the treatment provided for the hyperthyroid syndrome. Moreover, seminal plasma elements, such as fructose, Zn, and Mg, did not correlate with sperm density, motility, or morphology.     

Malignant fibrous histiocytoma of the lung: prognosis and therapy of a rare disease. Report of two cases and review of the literature

On the basis of 2 own patients and 18 cases reported in the literature, clinicopathological features of primary malignant fibrous histiocytoma of the lung are reviewed. Of the 20 patients (age-range: 14-75 yrs; 13 male, 7 female), 14 underwent resection. Recurrences were noted in 7 of them. 8 patients were free of disease at least 8 months postoperatively, one having undergone successful pulmonary metastasectomy. Postresection disease-free survival ranged from 8 months to 10 years. Adjuvant chemotherapy or irradiation (3/14) did not influence postoperative outcome. After chemotherapy, irradiation or conservative measures alone (6/20) survival did not exceed 12 months; remissions were not reported. The course was fatal within 12 months in 9/20 cases due to distant metastasis or local growth. 1 patient died of tumour-associated hypoglycemia. Age, sex, localization of the tumor and histologic subtype did not influence prognosis. Small tumors, asymtomatic at time of detection probably carry a better prognosis than larger ones.     

化疗联合自体细胞因子诱导杀伤细胞治疗急性白血病的临床观察

目的评价化疗联合自体细胞因子诱导的杀伤细胞(CIK)治疗急性白血病(AL)的疗效。方法选择经化疗达完全缓解(CR)>6个月的AL患者41例。19例患者接受化疗联合自体CIK细胞治疗,22例接受同期单纯化疗作为对照组。CIK细胞治疗采用血细胞分离机大量采集患者的外周血单个核细胞,用抗CD3单抗、IL2、IFNγ培养10d,将细胞洗涤后经静脉于化疗后第一天回输给患者。结果CIK组19例患者化疗同时共接受52疗程CIK细胞治疗,每例患者平均接受2~3个疗程CIK细胞治疗。每疗程回输CIK细胞总数为(22~300)×109/L,平均(142±85)×109/L。4年持续CR(CCR)率CIK组为734%;单纯化疗组4年预期CCR率为273%。两者差异有统计学意义(P<0005)。接受≥3个疗程CIK治疗的10例患者至观察截止时均处于CCR,中位CCR期43个月(23~52个月);接受<3个疗程CIK治疗的患者4/9例复发。结论化疗联合自体CIK细胞治疗AL的CCR率明显优于单纯化疗;疗效与疗程有关,疗程≥3个患者的疗效优于疗程<3个的患者。