Debora Capelli

Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy

Objectives:  Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side‐effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side‐effect.

Salvage therapy with an outpatient DHAP schedule followed by PBSC transplantation in 79 lymphoma patients: an intention to mobilize and transplant analysis

Chemotherapy followed by autologous transplantation may be an efficient salvage treatment in malignant lymphomas. We investigated the feasibility, tolerability and efficacy of an outpatient schedule of dexamethasone, cytarabine and cisplatin (DHAP), followed by peripheral blood progenitor cell autografting as salvage treatment in patients with high grade (HG), low grade (LG) non‐Hodgkins lymphoma (NHL) and Hodgkins Disease (HD). A total of 159 DHAP courses (median: 2, range: 1–5), was administered on outpatient basis to 79 patients (31 LG‐NHL, 28 HG‐NHL and 20 HD), with the intention to mobilize and to transplant. A successful collection was not achieved in 40% LG‐NHL, 10% HD and 20% HG‐NHL patients. The risk to fail the collection was significantly related to the number of previous chemotherapy courses (>6) (P = 0.005, RR = 1.4), to the pretransplant status (P = 0.04, RR = 13.5) and to the previous fludarabine administration (P = 0.01, RR = 20). High dose therapy (HDT) was feasible in 60 patients (76%). The overall treatment related mortality was 3.8%. The overall response rate (ORR) was 81% with a 57.6% overall survival (OS) at 62 months (95% CI: 45–69.3%) and a progression free survival (PFS) of 42% at 74 months (95% CI: 26.7–58%). The diagnosis of HG‐NHL and the non‐response to DHAP resulted to reduce respectively the OS (P = 0.007, RR = 2.8) and PFS probability (P = 0.01, RR = 4.1). In conclusion this outpatient schedule of DHAP is a well tolerated, efficient salvage and mobilizing regimen not only in HG‐NHL, but also in LG‐NHL and in HD. Randomized studies are needed to better define the role of DHAP in LG‐NHL and HD patients.

Long-term hematologic reconstitution after autologous peripheral blood progenitor cell transplantation: a comparison between controlled-rate freezing and uncontrolled-rate freezing at 80°C

BACKGROUND : The most widely used system for peripheral blood progenitor cell (PBPC) cryopreservation is controlled‐rate freezing (CRF). Uncontrolled‐rate freezing (URF) at –80°C has also been used, but its clinical impact has not been studied sufficiently yet.

Consolidation therapy for adult acute myeloid leukemia: A systematic analysis according to evidence based medicine

Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits “clinical trial” as publication type, “all adults 19+ years”, we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called “genetic randomization”). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.

Low-dose Gemtuzumab-Ozogamicin as post-consolidation therapy in elderly patients with acute myeloid leukaemia: a pilot study

T., Heldmann, K., Carmi, R., Parvari, R., Beit-Or, H., Goldman, B., Peleg, L., Levy-Lahad, E., Renbaum, P., Legum, S., Shomrat, R., Yeger, H., Benbenisti, D., Navon, R., Dror, V., Shohat, M., Magal, N., Navot, N. & Eyal, N. (1998) Prevalence of glucocerebrosidase mutations in the Israeli Askenazi Jewish poulation. Human Mutations, 12, 240–244. Pocovi, M., Cenarro, A., Civeira, F., Torralba, M.A., Perez-Calvo, J.I., Mozas, P., Giraldo, P., Girait, M., Myers, R.H., Cupples, L.A. & Ordovas, J.M. (1998) Beta –glucocerebrosidase gene locus as a link for Gaucher’s disease and familial hypo-alfa-lipoproteinaemia. Lancet, 351, 1919–1923.

Conditioning regimen with BCNU, etoposide, cytarabine and melphalan plus amifostine for outpatient autologous stem cell transplant: feasibility and outcome in 97 patients with lymphoma.

BEAM (BCNU, etoposide, cytarabine, melphalan) is standard conditioning for autologous stem cell transplant (ASCT) in Hodgkin disease (HD) and in non-Hodgkin lymphoma (NHL) [1]. Growth factors (GFs)...