High-dose therapy in multiple myeloma: effect of positive selection of CD34+ peripheral blood stem cells on hematologic engraftment and clinical outcome.

BACKGROUND AND OBJECTIVE: Positive selection of peripheral blood stem cells (PBSC) has been investigated in multiple myeloma (MM) with the aims of reducing plasma cell (PC) contamination of the leukaphereses and improving clinical outcome of autografted patients. DESIGN AND METHODS: In our center 39 untreated patients with stage II and III MM, younger than 65 years, started high-dose therapy consisting of 4 VAD cycles, collection of PBSC mobilized by 7 g/m(2) cyclophosphamide + G-CSF, and myeloablative treatment with 12 mg/kg busulfan plus 120 mg/m(2) melphalan. The leukaphereses from 23/39 patients (59%) were processed for positive selection of CD34(+) cells using an avidin-biotin immunoaffinity device. RESULTS: A reduction of PC contamination of as much as 2 log was found in the post-selection products by a flow-cytometric technique using the monoclonal antibody CD 138 alternatively coupled with CD38 and cytoplasmatic k or l light chains in separate samples. Hematologic reconstitution and clinical outcome of the 23 patients reinfused with selected CD34(+) cells (SEL group) were compared with those of the 16 patients reinfused with unselected cells (UNSEL group). No significant differences were observed between the 2 groups with regards to the median duration of neutropenia and thrombocytopenia, the hematologic support required, the incidence of febrile episodes and bacteremias. At a median follow-up of 18 months (range 5-34) after ASCT, there were 7/23 (32%) continuous complete remissions (CR) in the SEL group and 4/16 (25%) in the UNSEL group; there were 10/23 (44%) continuous partial remissions (PR) and 5/16 (31%) in the SEL and UNSEL groups, respectively. Two patients in the UNSEL group and one patient in the SEL group died of progressive disease. INTERPRETATION AND CONCLUSIONS: Our data show that positive selection allows rapid engraftment of hematopoiesis and low morbidity. Although no significant difference was detected between the two groups in the frequency of CR and PR 3 and 18 months after ASCT, a longer follow-up is needed to evaluate definitively the effect of CD34(+) selection on the clinical outcome after ASCT.

The therapy of primary adult systemic CD30-positive anaplastic large cell lymphoma: results of 40 cases treated in a single center.

The outcome of a series of adult patients, affected by primary systemic CD30-positive anaplastic large cell lymphoma (ALCL), treated with a sequential intensive therapeutic program, has been analyzed and all data available in the literature have been reviewed. Forty consecutive, unselected patients with ALCL were treated with the F-MACHOP regimen, followed by radiotherapy (RT) for residual mediastinal disease (15 cases) and by autologous stem cell transplantation (ASCT) conditioned with BAVC (29 cases). Eighty-nine percent (32/36) of the patients younger than 60 years were eligible for completing the sequential treatment. Since then, 3 patients in CR refused ASCT, 1 was excluded for cardiac toxicity and 3 progressed and died of disease. Thus, 29 have been so far submitted to the transplant procedure. CR and PR rates were 40% and 45% respectively after CHT; 52.5% and 35% after RT; 80% and 5% after ASCT, with 78% of patients transplanted in PR convertin to a CR. Actuarial overall survival is 85% at 48.5 months (93% at 66 months for the 29 transplanted patients) and disease free survival is 100% at 54 and 64 months respectively, with no relapses observed among patients who reached a CR. Considering our data and those of the literature, it can be concluded that although the role of ASCT in the therapy of ALCL must not be considered as definitive, its efficacy in converting PR into CR and in preventing relapses, suggests that a randomized trial comparing CHT alone vs CHT+ASCT should be undertaken.

Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha.

Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinical relevance is not yet completely defined. By using an IFN alpha antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was evaluated in 67Ph+ CML patients during IFN alpha 2a therapy at doses ranging from 6 to 9 MU/d. 15 patients (22%) developed nIFN alpha 2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically unresponsive to treatment. 52 patients did not develop antibodies and 11 of them (21%) were unresponsive. The negative relationship between the positivity for nIFN alpha 2a Abs and the response to treatment was highly significant (P = 0.0001). In nine nIFN alpha 2a Abs positive patients, treatment was changed from recombinant IFN alpha 2a to lymphoblastoid IFN alpha (IFN alpha-ly), at the same dose and schedule. After 9 months of IFN alpha-ly treatment a haematological response was achieved in 4/7 cases who were non-responsive to prior IFN alpha 2a therapy and was maintained in the other two patients previously responsive to IFN alpha 2a. However, no karyotypic response was observed. This data shows that a significant proportion of Ph+ CML patients receiving treatment with IFN alpha 2a can develop neutralizing antibodies and that these antibodies are associated with a loss of IFN alpha 2a efficacy. Changing the patients to treatment with lymphoblastoid IFN alpha may restore haematological response but it is not likely to induce a karyotypic response.