Vinorelbine plus intermediate dose cyclophosphamide is an effective and safe regimen for the mobilization of peripheral blood stem cells in patients with multiple myeloma.

High dose cyclophosphamide (HD-Cy) is commonly used to mobilize stem cells in multiple myeloma (MM). However, timing of collection is variable and incidence of side effects is substantial. We evaluated a combination of vinorelbine (VNB) (25 mg/m(2) day 1) plus Cy (1.5 g/m(2) day 2) and G-CSF as mobilizing regimen in 37 patients with MM. Results were compared to those achieved in 41 previously diagnosed patients mobilized with Cy at 4 g/m(2). Overall, 36/37 patients receiving VNB-Cy (97%) mobilized, as opposed to 40/41 (97%) in the controls (p:0.51). Median CD34+ cells peak was 94/mul for VNB-Cy patients and 96 for controls, p=0.36; median number of CD34+ cells collected was 9.2x10(6)/kg and 8.7x10(6)/kg, respectively (p=0.85). Median number of days to the highest CD34 count was shorter for VNB-Cy patients (nine vs 11, p=0.001). No VNB-Cy patient experienced grade 3-4 neutropenia and thrombocytopenia, as opposed to 63 and 19% in the controls (p=0.001 and 0.01, respectively). Hospitalization from toxicity was never required in VNB-Cy patients as compared to 19% in control group (p=0.01). We conclude that an outpatient combination of VNB plus intermediate dose Cy plus G-CSF is a safe, predictable, and highly effective mobilization regimen for patients with newly-diagnosed MM.

Fludarabine and cytarabine as continuous sequential infusion for elderly patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: A phase II study was conducted to investigate the effects of a therapeutic program based on the combination of fludarabine and cytarabine (ARA-C) administered as a sequential continuous infusion in untreated elderly patients with acute myeloid leukemia (AML). DESIGN AND METHODS: Sixty-three patients with non-M3 AML, median age 69 years (range 61-81), were accrued. Twenty-four patients (38%) had AML secondary to myelodysplastic syndrome. Fludarabine and ARA-C were administered as a continuous sequential infusion for 72 and 96 hours, respectively, after a loading dose. Patients achieving complete remission (CR) were intended to receive an additional course, followed by autologous stem cell transplantation (ASCT). RESULTS: Overall, 42 patients (67%) achieved CR. There were 10 induction deaths (16%), while 11 patients were refractory (17%). Among those achieving a remission, 35 patients (83%) received the planned consolidation course and 29 underwent mobilization of CD34+ cells into the peripheral blood for collection, which was successful in 23 (79%). Overall, 17 patients (27% of the whole population) received ASCT. The median overall and disease-free survival were both 10 months. INTERPRETATION AND CONCLUSIONS: Patients with an intermediate karyotype and those receiving ASCT had a significantly better clinical outcome. Results in terms of CR achievement, CD34+ cell collection and ASCT feasibility. A longer follow up is needed in order to evaluate the actual benefit on long-term survival.

High-dose idarubicin and busulphan as conditioning to autologous stem cell transplantation in adult patients with acute myeloid leukaemia.

Between 30 and 50% of patients with acute myeloid leukaemia (AML) relapse after autologous stem cell transplantation (ASCT). One possibility of reducing the relapse rate could be the adoption of conditioning regimens specifically designed for AML. We report treatment results achieved with a new conditioning for ASCT, based on high-dose idarubicin (IDA) plus oral busulphan. Patients (n = 40) were conditioned with a regimen consisting of 3 d continuous intravenous infusion IDA at 20 mg/m2, followed by 4 d conventional dose oral busulphan. Unpurged peripheral blood stem cells were used in all cases. All patients had non-M3-AML and were in first complete remission (CR). The median number of CD34+ cells infused was 6.9 x 10(6)/l (2.6-24). No case of transplant-related mortality occurred. In all cases, left ventricular ejection fraction remained unmodified after ASCT. Thirty-three of 40 patients (82%) had grade 3-4 mucositis requiring total parenteral nutrition in all cases. After a median follow up for surviving patients of 32 months from ASCT, 30 patients (75%) are alive and 26 (65%) are in continuous CR. Our data show that a conditioning regimen based on high-dose IDA plus busulphan results in an encouraging reduction of the relapse rate after ASCT in AML.

Ifosfamide, epirubicin and etoposide (IEV) regimen as salvage and mobilization therapy for refractory or early relapsing patients with aggressive non-Hodgkin's lymphoma.

The prognosis of early relapsing or refractory aggressive non-Hodgkin's lymphoma (NHL) is still poor. Effective salvage therapy should be able to induce high response rate as well as to mobilize hematopoietic precursors. A combination of ifosfamide, epirubicin and etoposide (IEV) was given to 28 patients with refractory or relapsing high grade NHL (4 lymphoblastic lymphoma and 24 large cell lymphoma). All patients were evaluated for response. After 2 courses of IEV, the overall and complete response rate were 64% and 39%, respectively. All patients were controlled for mobilization of peripheral blood stem cells, which was successful in 26 out of 28 (93%). Overall, 25 out of 26 patients proceeded to autologous stem cell transplantation (ASCT). Toxicity was mild, with no occurrence of severe persisting extra-hematologic side-effects. Following the entire therapeutic program, including IEV and ASCT, median progression free survival has not yet been reached and 21 patients are alive (18 in continuous complete remission) after a median follow-up of 18 months. Our results demonstrate that treatment with IEV regimen is effective in refractory or relapsing aggressive NHL, resulting in a high percentage of successful stem cell mobilization and feasibility of ASCT.

Outpatient-based peripheral blood stem cell transplantation for patients with multiple myeloma.

INTRODUCTION: There is a growing demand for autologous stem cell transplantation (ASCT) in newly diagnosed patients with multiple myeloma (MM), resulting in an increasing pressure on available hospital beds. In addition, more rational utilization of health resources should induce physicians to attempt therapeutic strategies aiming at reduction of costs. The aim of this study was to explore the feasibility and safety of performing ASCT on an outpatient basis, according to an early discharge method. MATERIALS AND METHODS: A total of 28 patients affected by MM and in complete or partial remission were selected to receive ASCT on an outpatient basis. In particular, after conditioning with high-dose melphalan and stem cell infusion, patients were programmed to go home and to be rehospitalized in the case of febrile neutropenia or other severe toxicities. RESULTS: All patients accepted the outpatient-based procedure. Out of 28 patients. 18 (64%) did spend the aplastic phase entirely at home following high-dose chemotherapy and stem cell infusion. A second hospital admission was required in 10 patients (36%). Febrile neutropenia and severe mucositis needing total parenteral nutrition were the most frequent causes of hospitalization. However, there were no documented infections and either fever or mucositis was easily resolved at the time of hematopoietic recovery in all patients. CONCLUSION: ASCT on an outpatient basis is feasible and safe in patients with MM. More than 60% of patients are manageable at home, provided that a caregiver is available.

Prolonged molecular remission after autologous stem cell transplantation in relapsed acute promyelocytic leukemia.

Six patients with relapsed acute promyelocytic leukemia (APL) received autologous stem cell transplantation (ASCT) in second (n=5) or fourth (n=1) molecular remission with a molecularly negative graft. After a median follow-up of 33 months from ASCT, 5 patients are alive in molecular remission and one died 27 months after autograft from refractory relapse.

Late relapse of acute promyelocytic leukemia treated with all- trans retinoic acid and chemotherapy: report of two cases.

Two patients with acute promyelocytic leukemia (APL) relapsed at 111 and 84 months after achievement of complete remission (CR) induced by a combination of all- trans retinoic acid and chemotherapy. In both patients molecular remission, obtained after consolidation, had been confirmed at 60 months from CR achievement. At relapse, morphological, immunophenotypic, cytogenetic, and molecular analyses showed findings identical to those at diagnosis. Hematological and molecular remission was induced with the identical treatment applied at diagnosis. We conclude that, although infrequently, patients with APL treated with modern combination therapy can experience very late relapse and can be rescued with treatment similar to that administered at diagnosis.

Fludarabine plus cyclophosphamide for the treatment of advanced chronic lymphocytic leukemia.

OBJECTIVES: Therapeutic results in advanced chronic lymphocytic leukemia (CLL) are still unsatisfactory in terms of complete remission achievement and duration, in spite of the extensive use of purine analogs. The objective of this study was to describe the clinical characteristics and treatment results from a series of 32 patients managed with a therapeutic program based on the combination of fludarabine and cyclophosphamide (CTX). METHODS: Thirty-two patients (median age 63 yr, range 42-75 yr) with newly diagnosed (47%) or refractory-relapsed (53%) CLL were programmed to receive six courses of a 3-d combination of fludarabine at 30 mg/m2/d plus CTX at 300 mg/m2/d. Refractory-relapsed patients had previously received different chemotherapy lines from 1 to 5. RESULTS: Fourteen of 32 (44%) patients achieved a complete remission, 16 (50%) obtained partial remission and two (6%) failed to respond. The CR rate was higher in untreated patients; in particular, CR was achieved in nine of 15 (60%) newly diagnosed cases as opposed to five of 17 (29%) among pretreated patients. Toxicity was caused by myelosuppression and/or infections in most cases. After a median follow-up of 24 months (range 8-48 months), 20 of 32 patients (62%) are alive, and 14 of 32 (44%) are free from progression. Median overall survival and median time to progression were 35 and 25 months, respectively. CONCLUSION: The combination of fludarabine with CTX is effective in advanced CLL with acceptable toxicity, either as first-line therapy or in refractory-relapsed patients. In particular, a considerable rate of complete remission can be achieved in untreated patients. Myelosuppression represents the major side-effect.

Complete remission induced by G-CSF in a patient with acute myeloid leukemia with t(8;21)(q22;q22).

We describe a case of acute myeloid leukemia (AML) with t(8;21) in which complete remission (CR) was obtained with G-CSF given at 10 microg/kg in the absence of concomitant cytotoxic chemotherapy. CR was achieved following 2 weeks of therapy and confirmed by investigating minimal residual disease by four-color flow cytometry analysis. During treatment with G-CSF, maturing cells with cytoplasmic Auer Rods were observed in the peripheral blood, suggesting a differentiation effect. This case adds further evidence for a specific role of G-CSF in the treatment of AML with t(8;21), namely in patients who are not eligible for aggressive chemotherapy.

Macroamylasemia in a patient with multiple myeloma.

We report a rare case of a patient with multiple myeloma who developed hyperamylasemia not associated to hyperamylasuria and without symptoms of pancreatic or salivary disease. This condition suggested the occurrence of macroamylasemia, consisting of macromolecules of amylase bound with immunoglobulins, which are not filtered by the kidneys. Hyperamylasemia was not present at the diagnosis of myeloma and appeared at the relapse of the disease, simultaneously with the appearance of an additional gamma-chain oligoclonal component, suggesting a possible role of these chains in producing macroamylasemia. To our knowledge, this is the first report of macroamylasemia in a patient with multiple myeloma.

De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine, cytarabine and G-CSF (FLAG).

OBJECTIVES: To evaluate therapeutic results and prognostic factors from a series of 44 patients affected by de novo acute myeloid leukemia with multilineage dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G-CSF (FLAG). METHODS: Forty-four patients with de novo MD-AML were treated with the FLAG regimen. The median age was 61 yr (range 31-75 yr). Induction therapy consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine. Patients with a compatible donor and aged less than 55 yr were programmed to receive allogeneic bone marrow transplantation (BMT), while in those without a donor and aged less than 65 yr autologous transplantation with peripheral blood stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone marrow harvest was performed in poor mobilizers. RESULTS: Complete remission (CR) was achieved in 28 out of 44 patients (64%). Death in induction occurred in four patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of consolidation was negligible. Most patients aged less than 60 yr and achieving CR were eligible for transplantation procedures, the main reason of exclusion being early relapse. Median overall survival and disease free survival were 16 and 22 months, respectively. Unfavorable cytogenetics was the only parameter significantly related to inferior clinical outcome following multivariate analysis. CONCLUSION: Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures.

High-dose cytarabine as consolidation treatment for patients with acute myeloid leukemia with t(8;21).

Seventeen patients affected by acute myeloid leukemia (AML) with t(8;21) were prospectively programmed to receive three courses of high-dose cytarabine (HDARA-C) as post-remission therapy. The median age was 39 years and in all cases t(8;21) was the only karyotypic abnormality. Complete remission (CR) was achieved in 14 out of 17 cases (82%) and, after first consolidation with NOVIA regimen (intermediate dose ARA-C plus mitoxantrone), all patients received the three planned courses of HDARA-C (3g/m(2) q12h on days 1, 3, 5). There were two documented infections, while all patients experienced fever of unknown origin (FUO). Nonhematological toxicity was mild. Thirteen out of 14 patients are in continuous CR after a median follow-up of 44 months. One patient relapsed at 16 months and, following CR2 achievement, underwent allogeneic transplantation; he died 3 months later while in CR from acute graft versus host disease (GVHD). Survival at 5 years is projected at 79%. Our data confirm the efficacy of repeated courses of HDARAC for patients with t(8;21) AML.