Maria Teresa Pirrotta

Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Rituximab 375 mg/m2 weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50×109/L) and complete responses (platelet count > 100×109/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3–18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose.

Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia

This randomized phase III clinical trial explored the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) in acute myeloid leukaemia (AML) patients aged >60 years. Three hundred and one AML patients were randomized to receive DNR (45 mg/m2 days 1–3) or DNX (80 mg/m2 days 1–3) plus cytarabine (AraC; 100 mg/m2 days 1–7). Patients in complete remission (CR) received a course of the same drugs as consolidation and then were randomized for maintenance with AraC+ all trans retinoic acid or no further treatment. Among 153 patients in the DNR arm, 78 (51·0%) achieved CR, 55 (35·9%) were resistant and 20 (13·1%) died during induction. Among 148 patients in the DNX arm, 73 (49·3%) achieved CR, 47 (31·8%) were resistant and 28 (18·9%) died during induction. Univariate analysis showed no difference as to induction results. After CR, DNX showed a higher incidence of early deaths (12·5% vs. 2·6% at 6 months, P = 0·053) but a lower incidence of relapse beyond 6 months (59% vs. 78% at 24 months, P = 0·064), with a cross in overall survival (OS) and disease‐free survival (DFS) curves and a later advantage for DNX arm after 12 months from diagnosis. DNX seems to improve OS and DFS in the long‐term follow‐up, because of a reduction in late relapses.

Imatinib does not impair specific antitumor T-cell immunity in patients with chronic myeloid leukemia

Imatinib does not impair specific antitumor T-cell immunity in patients with chronic myeloid leukemia

Unusual discordant responses in two multiple myeloma patients during bortezomib treatment.

Background: Cases of discordant responses in multiple myeloma (MM) patients after thalidomide therapy have been sometimes reported, in which extramedullary masses progress or present de novo with a simultaneous serum monoclonal protein reduction. Patients and Methods: We hereby report, for the first time, on two cases of MM patients with extramedullary myeloma localizations that developed during Velcade (bortezomib, PS341) treatment with a concomitant serum monoclonal protein reduction. Results: We observed in both patients a very good response in the serum monoclonal protein level, while extramedullary lesions appeared in the central nervous system and subcutaneously. Conclusions: We discuss pharmacokinetics of bortezomib and physiopathology of this unusual event and review the literature.

Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c-KIT positive acute myeloid leukemia. Results of an italian multicentric phase II study.

We evaluated safety and efficacy of imatinib (600 mg) in 36 c-KIT+ acute myeloid leukemia patients not amenable to receive conventional chemotherapy. No patient achieved complete remission. One patient obtained a hematologic improvement (platelet increase with transfusion independence). Median overall survival was 3 months (0.5–44+). Non-hematologic toxicity was overall mild.

Massive intravascular hemolysis: a fatal complication of Clostridium perfringens septicemia in a patient with acute lymphoblastic leukemia

Vaiopoulos et al. [1] described a case of massive intravascular hemolysis secondary to Clostridium perfringens septicemia in a patient with acute myeloid leukemia. We report a similar case of a 50-year-old male with acute lymphoblastic leukemia relapsed after 4 years from allogenic bone marrow transplantation. The diagnosis was confirmed by peripheral blood and bone marrow studies; the bone marrow was infiltrated (90%) by blast cells that appeared to be lymphoblasts on cytology. Immunophenotyping showed positive expression of CD19, CD10, CD22, HLADR, CyIgM and TdT in lymphoblasts. A conventional cytogenetic analysis was performed on short-term unstimulated bone marrow cultures. Chromosomal abnormalities were described according to the International System for Human Cytogenetic Nomenclature (ISCN) [2]. The karyotype showed: 46,XY [11]; 47,XY, – 2, – 3,t(2; 6)(q12; q13), + 7, + 11, + 12, – 13, – 14, – 15, + 21, + 22, +mar [9]. The patient started a re-induction program and received 2 doses of vincristine, 1 of cyclophosphamide and a daily high dose of methylprednisolone. On day 9 after the start of therapy, while he was neutropenic, he developed diarrhea and mild fever. Two days later severe anemia was evident with a marked reduction in serum hemoglobin level down to 3.5 g/dl. On the blood sample, the serum appeared bright red and a peripheral blood smear revealed microspherocytosis, indicating intravascular hemolysis. Serum biochemistry showed increased creatinine and lactate dehydrogenase levels and the aptoglobin level was below measurable standards. Hemoglobinuria was also present. Suddenly the patient developed hyperkalemia with cardiac failure and shock, and unfortunately died within a few hours. Clostridium perfringens was isolated from all blood and stool cultures taken. We agree with Vaiopoulos et al. [1] about the possibility, in neutropenic patients, of Clostridium perfringens producing hemolysine sepsis with massive intravascular hemolysis. According to the literature, such a complication, with a few exceptions, seems restricted to acute myeloid leukemias [1]. However, we would like to add that this pattern can also be observed in acute lymphoblastic leukemia, even if the neutropenic condition can be considered the main predisposing factor. Furthermore, we suggest promptly starting empiric antibiotic therapy at the beginning of mild fever in patients treated with high-dose corticosteroids, as this therapy could hide systemic signs of infection.

Thrombotic microangiopathy and occult neoplasia.

Thrombotic thrombocytopenic purpura (TTP), which is typically characterized by fever and central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is a prominent feature are the most common thrombotic microangiopathies (TMAs). TTP is usually associated with a severe deficiency of ADAMTS13 [a metalloproteinase involved in the degradation of von Willebrand factor (vWF) multimers], causing excessive accumulation of ultra-large vWF multimers and platelet aggregation with organ failure. By contrast, patients with HUS or other TMAs usually display a normal or at least detectable ADAMTS13 activity. A TMA may be occasionally developed in association with HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome, infections, cancer and bone marrow transplantation. In cancer patients, TMA may be related to chemotherapeutic regimens or the malignant disease itself. Occasionally, TMA is the first manifestation of an occult cancer, and in large series approximately 3% of patients who were originally diagnosed with TTP, were in fact harboring an occult malignancy. The pathogenesis of cancer-associated TMAs is not completely elucidated, but probably the most important factor is endothelial damage. However, cancer-associated TMAs show some distinct features that should promptly lead to complementary investigations for an underlying malignancy. Weakness, cough and dyspnoea, fever, weight loss, bone and abdominal pain are the most common presenting symptoms. Generally, biochemistry reveals markedly increased LDH levels, increased alkaline phosphatase and the blood smear shows erythromyelemia. Bone marrow biopsy is a valuable tool in order to establishing malignant seeding. Treatment of the underlying neoplasia is the mainstay of therapy and there is no role for plasmapheresis or plasma infusions.

Pilot study of gemtuzumab ozogamicin (GO), fludarabine, cytarabine and idarubicin combined regimen (GO-FLAI) as first-line induction therapy plus GO alone as consolidation therapy for elderly acute myeloid leukemia patients

The GO-FLAI regimen was used to treat 10 sequential patients meeting the following eligibility criteria: age 1 65; diagnosis of de novo or secondary AML; performance status (PS) ̂ 1. The clinical characteristics of the enrolled patients are described in table 1 . Briefly, 5/10 patients presented with ‘de novo’ disease, while 5 had leukemia progressing from a preexisting myelodysplastic syndrome. The median age was 72 years (range 65–77). Two cycles of fludarabine 25 mg/m 2 plus arabinosyl-cytosine 1 g/m 2 and idarubicine 5 mg/m 2 for 3 days and GO at 3 mg/m 2 on the fourth day were planned. As consolidation treatment, patients achieving a CR or partial remission (PR) received 2 monthly courses with GO at 3 mg/m 2 (first 4 patients) and 6 mg/m 2 (patients enrolled thereafter). After induction regimen, 6/10 patients reached a CR (60%), 2/10 (20%) obtained a PR and 2/10 (20%) were resistant to the treatment ( table 1 ). The most common adverse events at this stage of treatment were fever and chills during the administration of GO, infections secondary to neutropenia (66%) and transient grade I/II gastrointestinal and liver toxicity, the latter limited to aspartate transaminase (AST) and alanine transaminase (ALT) elevation. No hepatic veno-occlusive disease nor grade III/IV bleeding were recorded. The median time to recovery from severe neutropenia (absolute neutroThe prognosis of acute myeloid leukemia (AML) in older adults is generally poor. Standard cytotoxic chemotherapy is scarcely tolerated and usually followed by a complete remission (CR) rate of about 44–77% with a remission duration usually less than 1 year [1, 2] . On the other hand few prospective randomized studies including either conventional chemotherapy or newly discovered agents have been performed in this peculiar patient population. Recently, gemtuzumab ozogamicin (GO), an anti-CD33 antibody conjugated to calicheamicin, has been introduced in the treatment of AML patients as single agent [3–5] . In addition, some encouraging data have also been reported on GO associated with conventional chemotherapy [6–8] , including the combination of fludarabine and arabinosyl-cytosine albeit in the setting of younger AML patients [9] . However, the role of this antibody-targeted therapy as single agent in the postinduction treatment has not yet been defined. We here report a pilot experience on the feasibility and outcome of an age-adjusted combination regimen with GO, fludarabine, arabinosyl-cytosine and idarubicine (GO-FLAI regimen) followed by 2 courses of GO alone as consolidation treatment in a group of elderly AML patients. As induction, GO was administered at the end of a FLAI regimen at the low dose of 3 mg/m 2 , while as consolidation we planned to explore 2 different dose schedules of GO. Received: November 8, 2006 Accepted after revision: January 18, 2007 Published online: March 26, 2007

Low-dose thalidomide-induced agranulocytosis in a multiple myeloma patient treated at diagnosis.

Thalidomide represents a recent and innovative therapeutic approach in multiple myeloma. Main toxicity usually consists in somnolence, constipation, peripheral neuropathy and deep vein thrombosis, but, unlike alkylating agents, thalidomide is reported to rarely induce severe hematologic toxicity. The majority of patients developing neutropenia are heavily pretreated with three or more lines of chemotherapy. Here, we report, for the first time, clinical and laboratory data of a 66-year-old female patient with multiple myeloma at diagnosis who, after 4 weeks of thalidomide treatment, developed a grade 4 WHO neutropenia with septicemia. A brief review of the literature and suggestions for possible predictive factors of this toxicity are made.