Haifei Chen

Extramedullary plasmacytoma in the presence of multiple myeloma: clinical correlates and prognostic relevance

Objective We studied the clinical and laboratory features and outcomes of multiple myeloma (MM) with extramedullary plasmocytoma (EP) disease both at diagnosis and during the course of MM. Patients and methods Forty-two patients of 467 patients with MM were retrospectively analyzed from both the 100th Hospital of the People’s Liberation Army and Shanghai Changzheng Hospitals. The clinical characteristics, laboratory parameters, responses, risk factors, and outcomes were analyzed. Results The median age was 53 years with a male/female sex ratio of 34:8. Twenty-six patients had EP disease at the time of diagnosis, and 16 patients developed EP during the course of the disease. We found that the Durie–Salmon stage, serum lactate dehydrogenase level, beta-2-microglobulin, complete blood counts, albumin, and the type of immunoglobulin (Ig) were not associated with the development of EP disease. Patients who developed EP during the course of MM had a higher ratio of plasmocytes and premature plasmocytes in the bone marrow with lower C-reactive protein level and earlier stage of International Staging System for Lung Cancer at the diagnosis of MM compared with patients who presented with EP at diagnosis. Once the patients developed EP disease, they frequently showed resistance to chemotherapy. With a median follow-up of 30 months, 19 patients were alive. Log-rank univariate analysis showed that patients with EP who had normal C-reactive protein, higher hemoglobin, lower serum lactate dehydrogenase, and stage I of International Staging System for Lung Cancer had longer survival. However, cyclooxygenase multivariate analysis failed to show statistical significance for any factor. Conclusions EP disease is the MM end-phase and is not a rare manifestation of MM with a cumulative incidence of 9% of MM. The prognosis is very poor once the diagnosis of EP disease is concurrent with MM.

Valproic acid-associated low fibrinogen and delayed intracranial hemorrhage: case report and mini literature review

A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.

Clinical study of thalidomide combined with dexamethasone for the treatment of elderly patients with newly diagnosed multiple myeloma.

OBJECTIVE To investigate the relationship between the efficacy and safety of different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiple myeloma (MM). METHODS Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groups according to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overall response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) were compared between the two groups. RESULTS A total of 28 patients were followed up with a median of 18 months. The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS values were not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patients with a grading above 3 in group B was significantly higher than in group A (P=0.033). CONCLUSIONS The TD regimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM. TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas with financial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.

Efficacy and safety of immunosuppressive therapy in the treatment of seronegative hepatitis associated aplastic anemia

Objective To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA) (SNHAA) and hepatitis B virus (HBV) infection complicating AA (HBVAA), and thereby compare the efficacy of immunosuppressive therapy (IST). Methods An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes. Results Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60%) of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00), a quicker response to IST (2.5 months versus 4.5 months, P=0.018), a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03), and lower white blood cell and absolute neutrophil count (0.8×109/L versus 1.23×109/L and 0.26×109/L versus 0.58×109/L, P=0.026 and P=0.0009, respectively). No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. Conclusion The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly. Neither hepatitis prior to AA nor AA complicating HBV infection have been shown to influence the early efficacy of IST and adverse events, and HBV may not be the causative agent of AA.

Rituximab as first-line treatment for acquired thrombotic thrombocytopenic purpura:

Objective To investigate the efficacy and safety of rituximab (RTX) as first-line treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Methods Twenty-five patients with acute aTTP and/or severe a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency were admitted to our centre from April 2009 to March 2015. Fourteen patients received RTX plus standard therapy (plasma exchange and corticosteroids) at acute episodes. Haemoglobin, platelet count, schistocytes, lactate dehydrogenase levels, ADAMTS13 activity and its inhibitors, and the ratio of B lymphocytes in the peripheral blood, were monitored. The number of plasma exchange (PEXs), total plasma volume, remission time, relapse ratio, and adverse effects were recorded. Results The median number of PEXs was 5 (2–17) sessions and median total plasma volume was 168.43 ml/kg (62.86–469.52 ml/kg). Patients achieved haematological remission at a median of 15 days (5–22 days), and the median time of immunological remission was 2 weeks (2–8 weeks) with a median follow-up of 13 months (3–61 months). ADAMTS13 activity significantly increased after 2 weeks. The B lymphocyte percentage in peripheral blood was reduced 1 week after the first dose of RTX infusion compared with before treatment (2.21% ± 5.23% vs 18.47% ± 7.34%, P = 0.000 [the result of statistical software]), and began to gradually increase 9 months later. Severe adverse effects and relapsing TTP were not observed during therapy and follow-up. However, one patient who had sustained immunological remission died of severe pneumonia 7 months later. Conclusion Although our study was limited by its small sample number and it was a non-controlled, clinical trial, it showed potential benefits of RTX therapy for acute aTTP. RTX may be administered as a first-line therapy for lowering patients’ relapse rate in the long term. Randomized, controlled trials of RTX for aTTP are required.

Haematidrosis associated with epilepsy in a girl successfully treated with oxcarbazepine: Case report

The aetiology and pathological mechanisms involved in the development of haematidrosis (bloody sweat) remain unclear. There is no specific treatment for this disorder. This case report describes the clinical manifestations and treatment of a 9-year-old female with haematidrosis associated with epilepsy. The diagnosis of haematidrosis was confirmed by medical personnel who observed the bleeding and were able to rule out other causes of the bloody exudate. The episodes of bleeding were spontaneous, transient, and self-limited. Smears of the bloody exudate contained all of the components of peripheral blood. A skin biopsy taken at one site of the bloody exudate was normal, showing no signs of blood extravasation or bleeding sweat glands. The bleeding events were found to be immediately preceded by tonic seizures. An electroencephalogram indicated cerebral parietooccipital epilepsy, which was characterized by an intermittent medium-high amplitude θ rhythm (5–7 Hz) with a few spikes. The symptoms of both epilepsy and haematidrosis resolved after treatment with the antiepileptic drug 150 mg oxcarbazepine, orally, twice a day, which suggests that the epileptic seizures triggered haematidrosis in this patient.

Development of acquired factor V inhibitor after treatment with ceftazidime: a case report and review of the literature

We report the case of a 59-year-old Chinese man who showed an asymptomatic coagulation factor V deficiency pattern after second intravenous treatment with ceftazidime. Normal pooled plasma failed to correct the abnormalities in a mixing test, and the presence of factor V inhibitor was confirmed by the Bethesda method. The coagulopathy was not corrected by transfusion of fresh frozen plasma and prothrombin complex concentrate, but rather by treatment with prednisone and withdrawal of dubious drugs. The findings reported here should prompt clinicians to watch for drug-induced coagulation factor deficiency.

Effective treatment with para-aminomethylbenzoic acid for chronic disseminated intravascular coagulation associated with aortic dissection.

Chronic disseminated intravascular coagulation is a rare complication of aortic dissection. Surgical correction or low molecular weight heparin is treatment of choice, but for a severe bleeding problem due to excessive fibrinolysis, para-aminomethylbenzoic acid would be a simple and effective therapeutic approach.

Clinical and Therapeutic Studies of Acquired Thrombotic Thrombocytopenic Purpura in China

Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disorder mediated by autoantibodies against ADAMTS13. In this report, we study the clinical features, laboratory aberration, and treatment effect of 55 patients with acquired TTP in China. The classic pentad occurred in only 33% of TTP patients. Severe ADAMTS13 deficiency was detected in 85% of patients. Advanced age and hyperbilirubinemia might be risk factors for poor prognosis. Early and sufficient plasma exchange is the most important approach. The addition of rituximab to plasma exchange and corticosteroids appears to be effective in inducing and sustaining long-term remission in TTP, and is suitable to be administrated during the first episode. However, more optimal therapeutic regimen warrants further investigation to treat refractory cases and to reduce relapse rate.