Management of mobilization failure in 2017

In contemporary clinical practice, almost all allogeneic transplantations and autologous transplantations now capitalize on peripheral blood stem cells (PBSCs) as opposed to bone marrow (BM) for the source of stem cells. In this context, granulocyte colony-stimulating factor (G-CSF) plays a pivotal role as the most frequently applied frontline agent for stem cell mobilization. For patients classified as high-risk, chemotherapy based mobilization regimens can be preferred as a first choice and it is notable that this also used for remobilization. Mobilization failure occurs at a rate of 10%–40% with traditional strategies and it typically leads to low-efficiency practices, resource wastage, and delayed in treatment intervention. Notably, however, several factors can impact the effectiveness of CD34+ progenitor cell mobilization, including patient age and medical history (prior chemotherapy or radiotherapy, disease and marrow infiltration at the time of mobilization). In recent years, main (yet largely ineffective) approach was to increase G-CSF dose and add SCF, but novel and promising pathways have been opened up by the synergistic impact of a reversible inhibitor of CXCR4, plerixafor, with G-CSF. The literature shows to its favorable results in upfront and failed mobilizers, and it is necessary to use plerixafor (or equivalent agents) to optimize HSC harvest in poor mobilizers. Different CXCR4 inhibitors, growth hormone, VLA4 inhibitors, and parathormone, have been cited as new agents for mobilization failure in recent years. In view of the above considerations, the purpose of this paper is to examine the mobilization of PBSC while focusing specifically on poor mobilizers

Diagnosis of Large Granular Lymphocytic Leukemia in a Patient Previously Treated for Acute Myeloblastic Leukemia

Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia

Rituximab as salvage therapy for refractory sclerodermatous chronic graft-versus-host disease

While various different treatments have been suggested for the treatment of sclerodermatous graft-versus-host disease (ScGVHD), there is still no accepted standard for "salvage therapy" for refractory ScGVHD. We reviewed the clinical outcome of 14 patients suffering from refractory ScGVHD with refractory to at least 3 lines of immunosuppressive therapy and who received intravenous infusions of rituximab (375 mg/m2 per infusion) at weekly intervals for 4 weeks. Response to rituximab was evaluated after three months following the final infusion in accordance with National Institute of Health criteria. Median follow-up after rituximab was 20 months (range, 0.4-38.4 months). The overall response rate at was 43%. No major toxic events were seen related to rituximab. Rituximab appears to work well in the treatment of refractory ScGVHD and further trials in patients with early stage of this disease ought to be considered

An adult case of atypical hemolytic uremic syndrome presented with posterior reversible encephalopathy syndrome: Successful response to late-onset eculizumab treatment

Atypical hemolytic uremic syndrome is a rare and progressive disease caused by uncontrolled alternative complement activation. Dysregulation of the complement activation results in thrombotic microangiopathy and multiorgan damage. A 29-year-old woman who was admitted with complaints of vomiting and headache was detected to have acute renal failure with microangiopathic hemolytic anemia (MAHA). After the diagnosis of atypical hemolytic uremic syndrome (aHUS), she was treated with plasma exchange (PE) and hemodialysis (HD). She has experienced hypertension-related posterior reversible encephalopathy syndrome (PRES) at the second plasma exchange. She was initiated on eculizumab therapy because of no response to PE on the 34th days. Her renal functions progressively improved with eculizumab treatment. Dependence on dialysis was over by the 4th month. Dialysis free-serum Creatinine level was 2.2 mg/dL [glomerular filtration rate (e-GFR): 30 mL/min/1.73 m(2)] after 24 months

Assessment of ovarian reserve with anti-Mullerian hormone in women following allogeneic hematopoietic cell transplantation

Introduction: Severe ovarian failure and persistent infertility have could be seen in females following allogeneic hematopoietic cell transplantation (allo-HCT.) In this study, the authors aimed to determine the effectiveness of AMH on assessment of ovarian reserve in long-term survivors after allo-HCT. Material and Methods: Female patients, who underwent allo-HCT between August 2009 and February 2016, were retrospectively evaluated for ovarian capacity in long-term follow-up. Twenty-one female patients with a median age of 34 (22-45) years were included in the study. The serum levels of estrogen (E2), follicle stimulated hormone (FSH), luteinizing hormone (LH), and AMH were analysed. Results: The median duration of post-transplant follow-up was 37 (12-84) months. Primary ovarian failure (POF) was detected in eight (38,1%) and 19 (90,4%) cases in the pre-transplant and post-transplant period, respectively. It was found that no menstruation cycles were observed in 18 cases with low AMH levels. Discussion: Regular menstrual cycles may not guarantee the fertilization in the post-transplant period. Combined analysis of hormonal investigations, antral follicle count by vaginal USG, and evaluation of serum AMH levels may be preferred to demonstrate the presence of POF

Impacts of post-transplantation cyclophosphamide treatment after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Abstract Post-transplant cyclophosphamide has become a promising medical option after allogeneic HSCT. In this study we aimed to evaluate the efficacy of cyclophosphamide and cyclosporine combination in acute and chronic graft-versus-host disease (GvHD) prophylaxis in acute myeloid leukemia (AML) cases scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective analysis of data from 40 cases who underwent allogeneic HSCT under GvHD prophylaxis with cyclophosphamide and cyclosporine combination between April 2016 and August 2017 was made. Cyclophosphamide was given at daily doses of 50 mg/kg on post-transplant 3rd and 4th days, and cyclosporine was applied at daily doses of 3 mg/kg/day starting from the 5th post-transplant day. Cyclosporine dose was tapered beginning from the 45th postoperative day and completely discontinued on the 90th post-transplant day. Mean age was 38.25 ± 15.25 years. Posttransplant median follow-up was six months (6–17 months). Post-transplant, the number of deaths and mortality rates related and unrelated to transplantation were 5 (12.5%), and 2 (5%), respectively. Acute GvHD was diagnosed in 7 cases (17.5%), and relapse was noted in 9 cases (22.5%). Myeloablative or reduced intensity conditioning was performed in 22 (55%) and 18 (45%) patients, respectively. The distribution of the donors was as follows: match-related (n = 26; 65%), match-unrelated (n = 9, 22.5%) and haploidentical donors (n = 5; 12.5%). There was no statistically significant correlation between the transplant-related and unrelated mortality and parameters under investigation.Cyclophosphamide use appears to be a highly effective and promising strategy for acute GvHD prophylaxis in non-haploidentical allogeneic HSCT cases. Identification of the impact of cyclophosphamide use on the development of chronic GvHD needs further investigation

Biosimilar filgrastim (leucostim®) have similar efficacy in steady-state hematopoietic progenitor cell mobilization compared to original filgrastim (neupogen®) and lenograstim (granocyte®): A retrospective multicenter study

Biosimilar filgrastim (Leucostim®) was shown to be similar in terms of efficacy and safety in hematopoietic progenitor cell mobilization (HPCM) compared to originator filgrastim (Neupogen®) and lenograstim (Granocyte®) in healthy donors and chemomobilization settings. Here we report our retrospective experience with Leucostim® (n: 43) compared to Neupogen® (n: 71) and Granocyte® (n: 32) in steady-state mobilization of patients presenting with Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma. The median age of patients on Leucostim® (56) arm was significantly higher compared to patients who received Neupogen® (50) and Granocyte® (49) (p: 0.039). Patients who underwent HPCM with Leucostim® received less chemotherapy lines (p: 0.026) and courses (p: 0.046) compared to others. Otherwise the study cohort was homogenous in terms of gender, primary diagnosis and various risk factors for mobilization failure. Mobilization failure was defined as failure to achieve a minimum threshold (10/μL) for peripheral blood CD34+ cell concentration to initiate leukapheresis or 0.5 × 106/kg, 0.8 × 106/kg and 2 × 106/kg CD34+ cells in first, second and fourth days of apheresis, respectively. The study groups were similar in terms of median number of CD34+ progenitor cell yield (× 106/kg) (Neupogen®: 6.18, Granocyte®: 6.2 and Leucostim®: 6.2) (p: 0.959) and median number of leukapheresis sessions (p: 0.615). The treatment arms were also similar in terms of mobilization failure (Neupogen® 11.3% − Granocyte® 21.9% − Leucostim® 16.3%; p: 0.366). No patient experienced any severe adverse effect during HPCM. Leucostim® is equally effective and safe in HPCM compared to originator G-CSF (Neupogen®) and lenograstim (Granocyte®) in steady-state HPCM setting