Evaluation of erythrocytapheresis compared to phlebotomy in polycythaemia vera patients.

INTRODUCTION: Polycythaemia vera patients can present with arterial or venous vascular occlusive events such as thrombosis or cardiovascular disease; disease-related symptoms may significantly impact on the quality of life. The aim of this study was to evaluate the efficacy and safety of erythrocytapheresis compared to phlebotomy in the treatment of polycythaemia patients. METHODS: This study reports the findings of a retrospective analysis of 40 polycythaemia vera patients diagnosed according to published guidelines and treated either with erythrocytapheresis or phlebotomy over a four-year period. The goal of treatment was to reduce blood volume and red blood cell count to near normal levels as both of which may attenuate the symptoms and complications associated with polycythaemia. Patients were treated by applying a mathematical model. RESULTS: Using the model, 28 erythrocytapheresis procedures were performed. Blood laboratory values (red blood cell count, haemoglobin count and haematocrit level) were significantly reduced in patients treated with erythrocytapheresis. Moreover, among treated patients, erythrocytapheresis resulted in less work absenteeism and reduced costs due to lost production, with a lower overall procedure cost in comparison to phlebotomy. CONCLUSION: This model can assist in selecting the proper treatment modality for individual patients. Especially for those with high blood volumes and high achievable haematocrit levels (delta), erythrocytapheresis offers a more efficient method in red blood cell depletion compared to phlebotomy thereby, potentially reducing the number of treatment procedures required for the induction of polycythaemia vera patients as well as the interval between procedures during the maintenance phase.

Daratumumab as Single Agent in Relapsed/Refractory Myeloma Patients: A Retrospective Real-Life Survey.

BACKGROUND: The anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM. METHODS: This study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2-9). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020. RESULTS: The regimen was well tolerated with few grade 3-4 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm. CONCLUSIONS: Our findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.

Feasibility, Tolerability and Efficacy of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real-Life Survey of the Sicilian Myeloma Network.

Background: The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known about safety and efficacy of KRd outside a clinical trial context. Methods: Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers. Results: Median age was 62 years; patients had received a median of two previous lines of treatment (range 1-10) and 52% were refractory to previous treatment. Median number of KRd cycles was 12 (2-29), with a mean duration of treatment of 12 months; 21 patients had received at least 18 cycles. Overall response rate was 61%, including 18% complete response. Median PFS was 22.9 months, median OS was not reached. Creatinine clearance >30 mL/min, quality of the best achieved response and standard Fluorescence In Situ Hybridization (FISH) risk were independent predictors of favorable outcome. Patients who received the full-dosage of carfilzomib in the first two cycles had a better outcome. Conclusions: KRd was effective and well tolerated and in a considerable proportion of patients, therapy continued beyond the 18th cycle. The finding of a better outcome in patients with the higher cumulative dose of carfilzomib in the first two cycle encourages to maintain the maximum tolerated dose.

Early measurement of CD34+ cells in peripheral blood after cyclophosphamide and granulocyte colony-stimulating factor treatment predicts later CD34+ mobilisation failure and is a possible criterion for guiding "on demand" use of plerixafor.

BACKGROUND: Early identification of predictive factors of failure to mobilise CD34+ cells could enable rational use of plerixafor during first mobilisation, avoiding the need for a second mobilisation course. However, "on demand" administration of plerixafor needs to be driven by established parameters to avoid inappropriate use. MATERIALS AND METHODS: To address this issue, we studied the value of the peripheral blood CD34+ count, measured early (on days +10, +11, +12 and +13), in predicting the mobilisation outcome in the ensuing days. We retrospectively collected data from three Italian centres on 233 patients affected by multiple myeloma or lymphoma who underwent a first or second attempt at mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor. To assess the diagnostic value of peripheral blood white blood cell and CD34+ cell counts with respect to "mobilisation failure", we considered failed mobilisation as "disease" and the CD34+ cell count in peripheral blood, on a specific day, as a "diagnostic test". For various thresholds, we measured sensitivity, false positive rate, specificity and positive predictive value (PPV) as well as the area under the receiver-operating characteristic curves (AUC). RESULTS: A CD34+ cell count <10 × 10(6)/L on day 13 had high sensitivity (1.00) and high specificity (1.00) for predicting subsequent mobilisation failure, with an AUC of 1.0. However, good prediction was also obtained using a lower threshold (CD34+ cell count: <6 × 10(6)/L) at an earlier time (day 12). The PPV of the day 13 threshold was 1.00 while that of the day 12 one was 0.87. DISCUSSION: We propose that patients with <6 × 10(6)/L CD34+ cells in peripheral blood on day 12 and <10 × 10(6)/L on day 13 following mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor are candidates for "on demand" use of plerixafor, making the administration of this expensive agent more efficient and avoiding its inappropriate use.

Chemosensitivity of nonleukemic clonogenic precursors in AML patients in complete remission: association with CD34(+) mobilization and with disease-free survival.

A high number of CD34(+) cells in the peripheral blood during mobilization in patients with acute myeloid leukemia (AML) in complete remission (CR) is associated with a high relapse rate. The variability in chemoresistance of normal bone marrow precursors has been hypothesized as explanation for the variable CD34 mobilization in AML. In 37 patients with AML in CR, we determined the chemosensitivity of bone marrow clonogenic precursors to maphosphamide and etoposide, which was then correlated with the degree of CD34(+) mobilization. In an enlarged set of 49 patients, we also studied the importance of chemosensitivity of marrow precursors for disease-free survival and relapse incidence. Significant correlations were demonstrated between the peak number of CD34(+) cells and residual growth of colony-forming unit granulocyte-macrophage (CFU-GM) after maphosphamide (R = 0.550; p = 0.0003) and after etoposide (R = 0.793; p = 0.0003). It was possible to identify three groups of AML patients based on chemosensitivity. The mean CD34(+) peak was 33 × 10(6)/L in the hyperchemosensitive group, 141 × 10(6)/L in the normochemosensitive (p = 0.03), and 379 × 10(6)/L in the chemoresistant group (p = 0.002). Failed CD34(+) mobilization was observed in 72% of the hyperchemosensitive group, 23% of the normochemosensitive group, and 0% of the chemoresistant group (p = 0.001). Hyperchemosensitivity of CFU-GM, together with a low platelet count, were independent factors important in the failure of CD34(+) cell mobilization. A disease-free survival significantly inferior to that of all other patients was associated with chemoresistance of CFU-GM (log rank, p = 0.030) and with chemoresistance of burst-forming unit erythroid (BFU-E) (log rank, p = 0.033). Chemoresistance of CFU-GM (p = 0.048) and BFU-E (p = 0.017) was also associated with increase relapse incidence. Nonleukemic nature of these precursors was demonstrated studying minimal residual disease from single colony cells. In conclusion, we found that hyperchemosensitivity of normal nonleukemic CFU-GM is associated with a high risk of CD34(+) cell mobilization failure, while a chemoresistant pattern in CFU-GM and BFU-E is associated with poor disease-free survival and increased cumulative incidence of relapse.

Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m(2) plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients.

We designed intermediate dose etoposide + G-CSF 16 microg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m(2) i.v. day +1, +2, +3) +G-CSF 16 microg/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/m(2) + G-CSF 10 microg/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 x 10(9)/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 microg/kg resulted in a maximum length of neutropenia (PMN < 0.5 x 10(9)/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.

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.