Ilaria Scortechini

Factors affecting successful mobilization with plerixafor: an Italian prospective survey in 215 patients with multiple myeloma and lymphoma

Although the efficacy of plerixafor in peripheral blood stem cell (PBSC) mobilization has been explored in several studies, factors associated with successful plerixafor mobilization after administration of granulocyte–colony‐stimulating factor (G‐CSF), with or without chemotherapy, have not been investigated. We analyzed data on PBSC mobilization from a large Italian database of lymphoma and myeloma plerixafor‐treated patients.

Multicenter Experience Using Total Lymphoid Irradiation and Antithymocyte Globulin as Conditioning for Allografting in Hematological Malignancies

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects.

Very Low Rate of Readmission after an Early Discharge Outpatient Model for Autografting in Multiple Myeloma Patients: An Italian Multicenter Retrospective Study

We analyzed the main modalities and clinical outcomes of the early discharge outpatient model in autologous stem cell transplantation (EDOM-ASCT) for multiple myeloma in Italy. EDOM-ASCT was employed in 382 patients, for a total of 522 procedures, between 1998 and 2012. Our study showed high homogeneity among centers in terms of inclusion criteria, supportive care, and in hospital readmission criteria. Overall, readmissions during the aplastic phase occurred in 98 of 522 transplantations (18.8%). The major extrahematological complication was neutropenic fever in 161 cases (30.8%), which required readmission in 76 cases. The incidence of severe World Health Organization grade 3 to 4 mucositis was 9.6%. By univariate analysis, fever, mucositis, altered renal function at diagnosis, second transplantation, and transplantation performed late in the course of the disease were significantly correlated with readmission, whereas fever, mucositis, altered renal function, and timing of transplantation remained the only independent predictors by multivariate analysis. Overall, transplantation-related mortality was 1.0%. No center effect was observed in this study (P = .36). The safety and low rate of readmission of the EDOM-ASCT in myeloma trial suggest that this strategy could be extended to other transplantation centers if a stringent patient selection and appropriate management are applied.

Autologous hematopoietic progenitor cell transplantation for multiple myeloma through an outpatient program

Introduction: There are considerable concerns regarding the appropriate use of health care resources to reduce costs and waiting lists associated with autologous hematopoietic progenitor cell transplantation (AHPCT). One of the strategies to reach this goal is outpatient-based (OpB) AHPCT. Areas covered: We reviewed all the reported experiences in this field and illustrated the various models of OpB AHPCT. Expert opinion: The role of high-dose melphalan (HDM) followed by AHPCT in the treatment of Multiple Myeloma (MM) continues to evolve in the novel agent era and the International Myeloma Working Group recommends that AHPCT should be offered at some point in the course of the treatment program for a medically fit patient. The relatively short neutropenia and the limited extra-marrow toxicity after HDM support the hypothesis that MM patients are the most suitable for outpatient transplant programs. Various models have shown that the procedure is feasible and safe and may highly contribute to shorten waiting lists and to considerably cut health costs, with an improvement of quality of life. Ideal candidates may be those who are asymptomatic and fully active, who have a full-time caregiver and who can reside within easy reach from the transplant center.

Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders

Summary:We compared the use of G-CSF plus EPO in a group of 32 multiple myeloma and lymphoma patients with historical controls receiving G-CSF alone. Haemopoietic reconstitution was significantly faster in patients receiving G-CSF+EPO (group B), with a median time of 10 days to achieve an ANC count >0.5 × 109/l, compared to 11 days in the historical group (A). The median duration of severe neutropenia (ANC count <100/ml) was significantly shorter in group B compared to group A; platelet counts >20 × 109 and >50 × 109/l were achieved at days +13 and +17, respectively in group B, compared to days +14 and +24, respectively, in group A (P=0.015, 0.002) patients. The transfusion requirement was reduced in group B, with 0 (0–6) RBC units and 1 (0–5) platelet unit transfused in group B vs 2 RBC (0–9) and 2 platelet units (0–8) in group A. Median days of fever, antibiotic therapy and hospital stay were reduced in group B (9.5 days vs 22). The mean cost of autotransplantation per group A patient was 23 988 Euro, compared with 18 394 Euro for a group B patient. Our study suggests that the EPO+G-CSF combination not only accelerates engraftment kinetics, but can also improve the clinical course of ASCT.

Italian consensus conference for the outpatient autologous stem cell transplantation management in multiple myeloma

Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT) worldwide. The safety and efficacy of reducing hospital stay for MM patients undergoing ASCT have been widely explored, and different outpatient models have been proposed. However, there is no agreement on the criteria for selecting patients eligible for this strategy as well as the standards for their clinical management. On the basis of this rationale, the Italian Group for Stem Cell Transplantation (GITMO) endorsed a project to develop guidelines for the management of outpatient ASCT in MM, using evidence-based knowledge and consensus-formation techniques. An expert panel convened to discuss the currently available data on the practice of outpatient ASCT management and formulated recommendations according to the supporting evidence. Evidence gaps were filled with consensus-based statements. Three main topics were addressed: (1) the identification of criteria for selecting MM patients eligible for outpatient ASCT management; (2) the definition of standard procedures for performing outpatient ASCT (model, supportive care and monitoring during the aplastic phase); (3) the definition of the standard criteria and procedures for re-hospitalization during the aplastic phase at home. Herein, we report the summary and the results of the discussion and the consensus.

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.

6q deletion detected by fluorescence in situ hybridization using bacterial artificial chromosome in chronic lymphocytic leukemia

Deletions of the long arm of chromosome 6 are known to occur at relatively low frequency (3–6%) in chronic lymphocytic leukemia (CLL), and they are more frequently observed in 6q21. Few data have been reported regarding other bands on 6q involved by cytogenetic alterations in CLL. The cytogenetic study was performed in nuclei and metaphases obtained after stimulation with a combination of CpG‐oligonucleotide DSP30 and interleukin‐2. Four bacterial artificial chromosome (BAC) clones mapping regions in bands 6q16, 6q23, 6q25, 6q27 were used as probes for fluorescence in situ hybridization in 107 CLL cases in order to analyze the occurrence and localization of 6q aberrations. We identified 11 cases (10.2%) with 6q deletion of 107 patients studied with CLL. The trends of survival curves and the treatment‐free intervals (TFI) of patients with deletion suggest a better outcome than the other cytogenetic risk groups. We observed two subgroups with 6q deletion as the sole anomaly: two cases with 6q16 deletion, and three cases with 6q25.2–27 deletion. There were differences of age, stage, and TFI between both subgroups. By using BAC probes, we observed that 6q deletion has a higher frequency in CLL and is linked with a good prognosis. In addition, it was observed that the deletion in 6q16 appears to be the most frequent and, if present as the only abnormality, it could be associated with a most widespread disease.

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)...

Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2–4 (3–4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.