Salvatore Leotta

Plerixafor on-demand combined with chemotherapy and granulocyte colony-stimulating factor: significant improvement in peripheral blood stem cells mobilization and harvest with no increase in costs.

To date, no prospective study on Plerixafor ‘on‐demand’ in combination with chemotherapy and granulocyte colony‐stimulating factor (G‐CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on‐demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G‐CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34+ cells in peripheral blood was reduced by ‘on‐demand’ strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34+ cells 2 × 106/kg decreased from 20·9 to 4·0% (P = 0·0001). The on‐demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a ‘bias‐adjusted set of controls’. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G‐CSF, the ‘on‐demand’ use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.

Acute promyelocytic leukemia during pregnancy: report of 3 cases.

Acute promyelocytic leukemia (APL) is characterized by onset at a young age and a life-threatening hemorrhagic diathesis, which is attributed to a disseminated intravascular coagulation (DIC)-like coagulopathy. The discovery of all-trans-retinoic acid has changed the course of APL treatment by reducing the onset of DIC and inducing a complete and durable remission in more than 90% of patients. The occurrence of APL during pregnancy is not a frequent event, but the management of these patients raises many therapeutic and ethical dilemmas and requires a careful clinical case evaluation of fetal and maternal risk, coagulation status, the parents’ wishes, and therapeutic options. Here we describe 3 patients with APL diagnosed during pregnancy. Clinical data and the therapeutic approaches are presented. In the discussion, we analyze clinical decisions and therapeutic options and compare our cases with those found in the literature. Int J Hematol. 2004;79:31-36.

Prognostic value of CD34+ peak in peripheral blood during mobilization in intermediate-risk AML patients treated in first CR by autologous or allogeneic transplantation.

Ninety-six AML patients in 1st CR were evaluated for peak CD34+ cell levels in peripheral blood (PB) during PBSC mobilization and harvest. Distribution of CD34+ cell peaks was determined and cases were grouped on the basis of 50th and 75th percentile: group A, those having a CD34+ cell peak ⩽70 × 109/L (n=48); group B, those having a CD34+ cell peak between 70 and 183 × 109/L (n=24); group C, those having a CD34+ cell peak >183 × 109/L (n=24). Irrespective of post-remission treatment received, group A had a disease free survival (DFS) of 73%, group B a DFS of 51% and group C of 30% (P=0.0003). In intermediate cytogenetic risk patients, those treated by autologous transplantation had a DFS of 68, 33 and 14% in the groups A, B and C, respectively, (P=0.01) whereas after allogeneic transplantation DFS was 87% in group A+B vs 50% in group C (P=0.009). The peak of CD34+ cells in PB, was an independent predictor for DFS in multivariate analysis.

AMD3100 for urgent PBSC mobilization and allogeneic transplantation from a normal donor after failed marrow harvest

AMD3100 for urgent PBSC mobilization and allogeneic transplantation from a normal donor after failed marrow harvest

CD34+ selected haematopoietic stem cell (HSC) not preceded by any immunosuppressive therapy as effective treatment for graft failure.

CD34+ selected haematopoietic stem cell (HSC) not preceded by any immunosuppressive therapy as effective treatment for graft failure

Inadvertent transplantation of haematopoietic stem cells carrying constitutional Robertsonian translocation from an apparently normal donor to an AML patient: a case report.

Inadvertent transplantation of haematopoietic stem cells carrying constitutional Robertsonian translocation from an apparently normal donor to an AML patient: a case report

Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m2 plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients

We designed intermediate dose etoposide + G-CSF 16 µg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m2 i.v. day +1, +2, +3) +G-CSF 16 µg/kg/day. Results of PBSC mobilization in these patients were compared with those of a group of 37 lymphoma patients mobilized using cyclophosphamide (CTX) at dosage of 4 g/m2 + G-CSF 10 µg/kg/die. Mean peak of CD34+ cells achieved in P.B. and total CD34+ cells harvested were higher in patients mobilized with intermediate dose etoposide (p = 0.003 and p = 0.004, respectively). After transplantation recovery of polymorphonucleate neutrophils (PMN) > 0.5 × 109/L did not differ significantly between groups: 11.7 days in intermediate dose etoposide group and 11.5 days in CTX group (p = 0.7). Intermediate dose etoposide + G-CSF 16 µg/kg resulted in a maximum length of neutropenia (PMN < 0.5 × 109/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 µg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.

Autologous Transplantation in 1st Cr Aml Patients with Purged or Unpurged Bone Marrow: Good Clinical Results in Favorable CytogeneticGroup and in those Infused with a Low Number of Marrow Cells

In a single institution, 31 patients affected with Acute Myeloid Leukaemia (AML) in 1st Complete Remission (CR) received autologous bone marrow transplantation (ABMT). Mafosfamide was employed in a non-randomized fashion to purge marrows, in 15 cases bone marrow cells were purged, while in 16 they were left unpurged. Dose of infused Total Nucleated Cells (TNC) was an important factor for myeloid engraftment (P=0.02). LFS was 58% in purged and 40% in unpurged groups (P=0.26). Patients having a good prognosis cariotype had a LFS of 100% while the group of all other patients had a LFS of 37.5%. Patients receiving a dose of TNC below to median had a LFS of 65% and those receiving a dose of TNC>median had a LFS of 28% (P=0.017). Purging significantly improved LFS in patients “not harbouring good cytogenetic abnormalities” (53% LFS in purged group versus 18% in unpurged group, P=0.05). In conclusion, ABMT is associated with excellent results in “good prognosis cytogenetic”. Purging may improve results in patients belonging to “intermediate cytogenetic group”. A high number of infused TNC produces a fast myeloid engraftment but a poor LFS.

Palifermin reduces infection rate and hyperfibrinogenemia in patients treated with high-dose chemotherapy based on beam or BU-thiothepa

We performed a retrospective study in patients who underwent high-dose chemotherapy and auto-SCT because of haematological malignancies. Forty patients were treated with palifermin while 80 were controls selected after being matched for diagnosis and length of neutropenia. Patients treated with BEAM or BU-CY or THIO-CY (BEAM/BUS) displayed, after palifermin, a lower rate of severe oral mucositis (P=0.03). This beneficial effect of palifermin was not evident in the stratum of patients treated with high-dose melphalan (HD-PAM). After palifermin, we observed in the whole treated population a reduced rate of ‘fever of unknown origin’ (FUO, P=0.02) and of severe infections not related to Gram-positive bacteria (FUO, Gram-negative bacteremia or pneumonia) (P=0.003). This effect of palifermin on infections not related to Gram-positive bacteria was evident only in patients receiving BEAM/BUS (P=0.01) and not in patients treated with HD-PAM (P=0.11). Fibrinogen peak in plasma was found to be reduced after palifermin in the whole population (P=0.01) and in the stratum who received BEAM/BUS (P=0.02) but not in the stratum of HD-PAM. In conclusion, anti-infectious beneficial effects of palifermin are more evident in BEAM/BUS-treated patients and toward some types of infections. Reduction of fibrinogen level after palifermin suggests that this agent reduces not only the rate of infections but also their severity.

Cost-effectiveness of on-demand plerixafor added to chemotherapy and granulocyte-colony stimulating factor for peripheral blood stem cell mobilization in multiple myeloma

Abstract We here report final results of a phase II/III prospective study that evaluated in Multiple Myeloma the use of on-demand plerixafor (PLX) added to mobilizing chemotherapy for patients showing predictive signs of mobilization failure. A total of 111 patients with MM were registered, all received cyclophosphamide 4 g/m2 and granulocyte colony-stimulating factor (G-CSF). Overall, a successful CD34+ cell mobilization was achieved in 97.2% (108/111) of patients. Minimum harvest (≥2.0 × 106 CD34+ cells/kg) was achieved in 97.2% (108/111) and optimal harvest success (≥4.0 × 106 CD34+ cells/kg) was achieved in 84.6% (94/111). Multivariate analysis showed that patients who received on-demand PLX treatment had significantly higher likelihoods of successfully achieving both the minimal (p = .006) and optimal harvest (p = .05) in respect to a historical control group mobilized without any PLX. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful minimal harvest, was €40.6 per patient.