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Clinical or biological parameters useful to predict progression during treatment in real‐life setting with ibrutinib, idelalisib and venetoclax in relapsed/refractory chronic lymphocytic leukemia (CLL) are still debated. We conducted a multi‐center retrospective study on CLL patients treated with ibrutinib and/or idelalisib who were switched to venetoclax for progression or due to adverse events to identify any clinical and/or biological parameters useful to predict progression during treatment with venetoclax. Of all the 128 evaluable patients, 81 had received ibrutinib prior to switching to venetoclax, 35 had received idelalisib and 12 both. When comparing the three subgroups, we did not notice any statistical difference in terms of clinical or biological features. No variable at baseline and at different time points during the follow‐up (at 6, 12, 18 and 24 months) was found to predict progression nor to have significance for Progression Free Survival (PFS) in the ibrutinib group and in the idelalisib group and in subgroups according to the line of treatment. Analyzing the data of the venetoclax treatment, after a median follow up of 14.3 months, median PFS was not reached and estimated 3‐year PFS was 54%. Of the 128 patients treated with venetoclax, 28 (22%) experienced progressive disease. At multivariate analysis for predictive factors for progression, lymph node diameter >56.5 mm before starting treatment emerged as an independent risk factor for progression. The lymph node predictive role for progression during venetoclax treatment could be a new parameter that deserves to be investigate in future studies. [ABSTRACT FROM AUTHOR]

Studies performed on mice and healthy human volunteers have shown that a single dose of pegfilgrastim (Peg-GCSF) is effective in stimulating peripheral blood stem cells (PBSC) mobilization. This prompted us to try the stimulation with pegfilgrastim in a patient previously non-mobilizing with a combination of chemotherapy and filgrastim. In December 2003, a 65-yr-old man was diagnosed as having stage III A IgG/k multiple myeloma. He received three courses of polichemotherapy (DC-IE ) obtaining a stable response. Afterwards, the patient was treated with high-dose cyclophosphamide (CPM; 7 g/sqm) plus daily 10 mcg/kg filgrastim in order to mobilize PBSC, without success. After 2 months off therapy, the disease progressed and the patient received alternate cycles VAD (vincristine, dexamethasone, adriblastine)/high-dose dexamethasone. A second attempt to mobilize PBSC, using daily 10 mcg/kg filgrastim after the second and third VAD cycle, failed. In a further attempt to mobilize PBSC, we administered a single dose of 12 mg pegfilgrastim on day 5 after a fourth VAD course. Daily evaluation of circulatory CD34+ cells was started from day 8 after the end of chemotherapy. On day +10 postchemotherapy the CD34+ cell count was 24/ μL and two aphaeresis were performed, harvesting 1.6 × 106 and 0.89 × 106 CD34+ cells/kg respectively (total 2.49 × 106 cells/kg). The only side effect was moderate skeletal pain. The patient underwent successful transplantation. The median times necessary to recover 0.5 × 109 PMN /L and 20 × 109 platelets/L after PBSC reinfusion were 9 and 12 d respectively. The patient did not need red blood cell or platelet transfusions. He experienced a sustained engraftment and maintains complete remission 9 months after the reinfusion. In conclusion, a single dose of pegfilgrastim was able to mobilize a sufficient number of CD34+ in a multiple myeloma patient not responsive to two previous attempts with high or standard dose chemotherapy followed by filgrastim. This approach, if confirmed on larger series and other diseases, could open new opportunities in stem cell mobilization for poor or non-mobilizers. [ABSTRACT FROM AUTHOR]

Mele A, Leopardi G, Sparaventi G, Nicolini G, D'Adamo F, Guiducci B, Barulli S, Malerba L, Stramigioli S, Talevi N, Politi P, Isidori A, Malagola M, Piccaluga P, Visani G. Mini-ICE effectively mobilises peripheral blood stem cells after fludarabine-based regimens in acute myeloid leukaemia.Eur J Haematol 2005: 74: 277–281.© Blackwell Munksgaard 2005.Fludarabine-based cycles severely impair mobilisation and collection of peripheral blood stem cells (PBSC) in acute myeloid leukaemia (AML). In an effort of reversing this side-effect, we studied the action on mobilisation and collection of PBSC of a low-dose regimen: 5-d Mini-ICE (oral idarubicin and etoposide; subcutaneous cytosine arabinoside) administered after fludarabine-based regimens in seven adult AML patients. Leukapheresis were started when the CD34+ cell count was more than 10/μL. The median number of harvested CD34+ cells was 8.1 × 106/kg (range 3.08–15.2). All the patients were successfully submitted to PBSC transplantation. Median times to neutrophil and platelet recovery were rapid with a normal transfusional support. We suggest that the Mini-ICE programme is feasible, well tolerated and effective in terms of PBSC mobilisation and collection in low-yield AML patients previously treated with fludarabine. It is well known that a negative effect on stem cell mobilisation and harvest is observed not only after fludarabine administration in AML or low-grade lymphomas, but also after cycles based on different agents, such as thalidomide in multiple myeloma. This preliminary experience, if confirmed on larger series and/or other haematological malignancies, could open new opportunities to perform autologous PBSC transplantation in heavily pretreated cases, allowing a full source of therapeutic options before the start of the mobilisation process. [ABSTRACT FROM AUTHOR]

Offidani M, Corvatta L, Marconi M, Malerba L, Mele A, Olivieri A, Brunori M, Catarini M, Candela M, Capelli D, Montanari M, Rupoli S, Leoni P. Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy. Eur J Haematol 2004: 72: 403–409. © Blackwell Munksgaard 2004. 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. Fifty-nine patients were treated with thalidomide alone or combined with oral melphalan. The median age was 69 yr. The initial dose of thalidomide was 100 mg/day increasing weekly by 100 mg increments until a maximum dose of 400 mg was attained. Melphalan was administered at a dose of 0.20 mg/kg/d for 4 d every 28 d. Nearly one-fourth of patients discontinued thalidomide because of toxicity. Constipation (71%), somnolence (36%) and fatigue (20%) were the most common side-effects and they were not dose dependent. Peripheral neuropathy occurred in 39% of patients and a thalidomide median daily dose of more than 150 mg was significantly associated with higher frequency and actuarial risk of peripheral neuropathy without improving the response rate. Deep venous thrombosis was observed in 7% of patients and other side-effects were rare. In patients with advanced multiple myeloma we found that a thalidomide daily dose of 150 mg minimizes peripheral neuropathy without jeopardizing response and survival. [ABSTRACT FROM AUTHOR]

The article offers information on the study by T. Weber and others, testing the enteric-coated mycophenolate sodium (EC-MPS) for reducing acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Topics include releasing of mycophenolic acid (MPA) in the intestine, absence of interaction between antiacids, and discussing the treatment of patients with gastrointestinal toxicities.

The author comments on a study by N. Blank and co-workers where they demonstrated the safety and efficacy of a low-dose cyclophosphamide regimen following by multiple G-CSF dosing for the mobilization of hemopoietic stem cells (HSCs) in patients with advanced automoimmune diseases (ADs). The study provides a rationale for reducing cumulative cyclophosphamide dose prior to high dose therapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT) in patients with ADs refractory.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)