Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or refractory multiple myeloma patients.

PURPOSE: The purpose of this study was to assess the efficacy and toxicity of DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin), as third-line regimen in relapsed or refractory multiple myeloma (MM) patients. PATIENTS AND METHODS: Twelve patients (11 men, 1 woman, aged 38-73 years, median 58) with relapsed or refractory MM received 28 cycles of DCEP. Eleven out of 12 patients had already failed 4-6 cycles of VAD (vincristine, doxorubicin, dexamethasone), 7/12 had received 2 or more lines of prior therapy and one of them had high-dose therapy with stem cell support. Seven out of 12 patients were candidates for megatherapy with autologous peripheral blood stem cells transplantation (ASCT) either as consolidation or as salvage treatment. Each cycle of DCEP consisted of cyclophosphamide 400 mg/m(2)/daily, cisplatin 15 mg/m(2)/daily and etoposide 40 mg/m(2)/daily as a 24h infusion, all three drugs administered on days 1-4; plus dexamethasone i.v. bolus 40 mg daily, days 1-4. The dose of cisplatin was adjusted in case of renal impairment. G-CSF was administered daily from day +5 to recovery. The course was repeated every 28 days or was delayed 5-10 days according to the patient's clinical condition. RESULTS: The regimen was well tolerated with no major adverse reactions, except for grade 3 or 4 myelotoxicity of short duration. Responses were assessed using the EBMT criteria after the second cycle. Two out of 12 patients achieved complete remission (CR) and 5/12 partial remission (PR), while 5/12 had no response (NR). The overall response (OR) was 58.3% with a median response duration 9 months (range 4-36). Four patients proceeded to successful peripheral blood stem cell mobilization and transplantation. CONCLUSIONS: DCEP is an effective and safe salvage treatment for relapsed or refractory MM patients which also offers the possibility for a successful peripheral blood stem cells collection in patients eligible for high-dose therapy and ASCT.

Clinical correlation of bone marrow microvessel density in essential thrombocythemia.

The aim of this study was to investigate the prognostic relevance of angiogenesis expressed as bone marrow microvessel density (MVD) in 40 patients with essential thrombocythemia (ET). Bone marrow MVD was visualized in paraffin tissue sections using immunohistochemical staining for CD34 protein. Increased MVD of bone marrow specimens was not significantly correlated with clinical (sex, age, microvascular disturbances, liver and spleen size, complications, treatment or no before biopsy), laboratory (peripheral blood count), bone marrow histopathological parameters (cellularity, megakaryocyte clumping and reticulin fibrosis) and overall survival. These preliminary findings suggest that angiogenesis has no prognostic value in patients with ET.

Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they are on regular follow-up. Two women after 10 and 14 months in PR developed acute leukemia and died. In conclusion, combination therapy with EPO, nandrolone decanoate and low-dose methylprednisolone may be effective as an alternative treatment for RBC transfusion-dependent patients with RA unresponsive to EPO administration alone.

Angiogenesis in chronic myeloproliferative diseases detected by CD34 expression.

Increased bone marrow angiogenesis estimated as bone marrow microvessel density (MVD), or as serum angiogenic factor levels and/or immunohistochemical expression of these factors in bone marrow biopsy has been demonstrated in a variety of hematological disorders including chronic myeloproliferative diseases (MPDs). The aim of this study was to investigate the MVD in 25 cases of myelofibrosis with myeloid metaplasia (MMM). MVD was estimated by CD34 immunohistochemical expression in bone marrow biopsies. A control group of 27 patients without bone marrow disease, eight cases of polycythemia vera (PV), 41 cases of essential thrombocythemia (ET) and nine cases of chronic myeloid leukemia (CML) were also studied. Moreover, in cases with MMM, MVD was correlated with clinical, laboratory, histological parameters and the outcome of the patients. Our study confirmed a significantly higher degree of angiogenesis in MMM, PV, ET and CML compared with controls (P < 0.001, P = 0.0007, P < 0.001 and P = 0.0008, respectively). Angiogenesis was higher in MMM than PV, ET and CML cases (P < 0.001, P < 0.001 and P = 0.008). Increased angiogenesis was correlated with hypercatabolic symptoms in MMM patients (P = 0.009). No correlation with other clinicopathological parameters or clinical outcome was found. However, definitive conclusions regarding the prognostic value of increased angiogenesis may require additional follow-up and a larger group of patients.

Solitary bone plasmacytoma in a young patient.

Plasma cell disorder, a disease of the elderly, is extremely rare in those below 30 years of age. A young 18 year old patient with solitary plasmacytoma is described in this case report.

Skin and gingival lesions in a young woman with B-prolymphocytic leukemia (B-PLL).

B-PLL has not been often associated with diffuse skin involvement or oral lesions. We present a 32 year-old woman in whom skin and gingival manifestations were the prominent clinical signs of disease relapse.

Preliminary results of amifostine administration in combination with recombinant human erythropoietin in patients with myelodysplastic syndromes.

Amifostine is a cytoprotective agent mainly used in cancer therapies, in order to ameliorate the toxic effects of anticancer chemotherapy and radiotherapy. In the past years an intriguing number of applications of amifostine have been identified; one of these is bone marrow cells protection and stimulation. Amifostine was administered in seven patients with myelodysplastic syndromes, four males and 3 females aged between 67 and 78 years old, in order to estimate its efficacy in reducing the need for red blood cells transfusions. Two patients had RAEB, four RA and one RARS. The drug was administered in an outpatient basis in a dose of 300 mgr/m2, three times weekly for at least four weeks. We administered at the same time erythropoietin 10.000 U subcutaneously. All patients received daily supplementation of oral ferrum sulfate and folic acid. Three patients, a woman with RA and two men, one with RA and another with RAEB improved the levels of Hb beyond 12,0 gr/dl and did not receive blood transfusions after the second week of treatment. The drug was well tollerated without any side effects in all of the patients.

A patient with essential thrombocytosis and multiple sclerosis.

We report on a patient with a 5-year history of essential thrombocytosis (ET) who developed multiple sclerosis (MS) during the last 5 months. The patient was treated for MS with interferon-beta (IFN-beta), which also had a beneficial effect on the ET. We describe the patient's history and the beneficial effect of IFN-beta administration in reducing the number of platelets. We also discuss the possible link between the pathogenesis of ET and MS.

Skin lesion's treatment with alfa interferon in a patient with B-CLL.

Treatment with recombinant alfa-2b-interferon in a patient with advanced B-CLL resulting in complete remission of skin lesions after one month therapy is reported in this paper. Interferon was administered subcutaneously three times weekly. Six months later while the treatment continued, the disease remained stable.

Severe muscle weakness due to hypokalemia as a manifestation of small-cell carcinoma.

We describe the case of a 56-year-old man with severe muscle weakness due to heavy hypokalemia (serum potassium 1.44 mmol/l) associated with inappropriate kaliuria and alkalemia. Subsequent investigation revealed the presence of ectopic ACTH hypersecretion due to a small-cell lung carcinoma. A significant clinical/laboratory improvement was achieved following chemotherapy-induced regression of the primary tumor. The profound hypokalemia was probably the result of cortisol hypersecretion, which in concert with the ACTH-induced decreased 11beta-hydroxysteroid dehydrogenase activity can exhibit an increased mineralocorticoid activity. In addition, other ACTH-dependent mineralocorticoids may play a contributory role in the development of severe hypokalemia.

Fractional excretion of magnesium in normal subjects and in patients with hypomagnesemia.

The aim of our study was the determination of fractional excretion of magnesium (FEMg++) in both normal subjects and hypomagnesemic patients. 142 subjects aged 26-72 years, recruited from our lipid clinic (control population) and 74 hypomagnesemic patients, aged 36-75 years, were studied. The mean FEMg++ in the control population was 1.8 per cent (range, 0.5-4 per cent). FEMg++ was not correlated with either serum magnesium or with serum creatinine. The mean FEMg++ in patients with hypomagnesemia of extrarenal origin was 1.4 per cent (range, 0.5-2.7 per cent), while the mean FEMg++ in hypomagnesemic patients in whom renal magnesium loss was the main etiologic factor for the pathogenesis of hypomagnesemia was 15 per cent (range, 4-48 per cent). In both groups of hypomagnesemic patients FEMg++ was positively correlated with the urinary magnesium to creatinine molar ratio, but was not correlated with serum magnesium or creatinine levels. FEMg++ could better distinguish the two groups of hypomagnesemic patients than the urinary magnesium to creatinine molar ratio. Hypomagnesemic patients exhibited a cluster of other acid-base and electrolyte abnormalities, mainly respiratory alkalosis, hypokalemia, hypophosphatemia, and hypocalcemia. In conclusion, in hypomagnesemic patients with normal renal function FEMg++ is a very useful tool for the diagnostic approach of hypomagnesemia. A value more than 4 per cent is indicative of inappropriate magnesium loss.