Elżbieta Urbanowska

Triple transplantation of autologous peripheral blood stem cells each time following conditioning with 100 mg/m2 of melphalan for multiple myeloma patients in poor performance status ☆

Approximately one third of multiple myeloma patients (below 60 years) are diagnosed either in advanced disease or with significant comorbidities. Many other patients referred to transplant centers have already been heavily pretreated with multiple courses of various conventional chemotherapies. These patients are frequently in bad or even grave clinical condition; they are unlikely to survive standard high-dose melphalan (200 mg/m(3)) chemotherapy and autologous hematopoietic stem cell transplantation. Palumbo et al reported a protocol for elderly patients that utilized reduced conditioning (melphalan 100 mg/m(2) three times at 2-month intervals, each time supported by autologous hematopoietic rescue). We have used this protocol as a start to develop a method to induce a remission in the aforementioned subgroup of myeloma patients. Patients with stage III disease and WHO performance status 2 or higher are treated with one or two cycles of cyclophosphamide (2 to 4 g/m(2)) and undergo peripheral blood stem cells collection. Subsequently, they are treated with three to four doses of melphalan (100 mg/m(2)) at 8- to 12-weeks intervals each time supported by infusion of peripheral blood stem cells. To date 13 patients have been entered into the protocol. With one exception of transiently stable disease, the remaining patients obtained at least partial remission and three, complete remission. The compliance was good and better with each subsequent course. For half of the patients the problem was a short duration of response. This method when developed may offer a new treatment alternative for a subgroup of high-risk multiple myeloma patients.

Bone marrow harvest from unrelated donors – up to date methodology

Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current “up‐to‐date” standard of the bone marrow harvest in unrelated stem cell donors.

Injection of G-CSF During Leukaphereses Reduces the Number of Aphereses Needed for Mobilization in Unrelated Hematopoietic Stem Cell Donors

BACKGROUND This is a single-center, retrospective study in the field of mobilization of hematopoietic stem cell from unrelated donors. We aimed to investigate whether delaying the last G-CSF dose after the start of apheresis influences its results. MATERIAL AND METHODS The medical records of 55 unrelated hematopoietic stem cell donors during the period 2010-2013 were analysed. In this series, 40 received donors the last G-CSF injection prior to the leukapheresis procedure, and 15 received the last injection after apheresis was initiated. RESULTS In the delayed G-CSF application group, more donors had already reached the requested cell number during first apheresis than in the group treated following the standard procedure (73% vs. 35%, respectively; p<0.01). Also, the average total G-CSF dose needed to mobilize the requested cell number was lower (41 µg/kg vs. 48 µg/kg, respectively, p=0.002). CONCLUSIONS Delayed G-CSF use in donors undergoing stem cell mobilization shows a better efficiency of stem cell mobilization.

Bone marrow harvest in donors with anaemia

Bone marrow harvest (BMH) for haematopoietic stem cell transplantation is a well‐established procedure. The guidelines of World Marrow Donor Association provide information on donor selection. However, some of the guidelines regarding donors with anaemia prior to harvest lack in supporting data from clinical studies. With this study, we aimed to provide such data.

Continuous Mononuclear Cell Collection (cMNC) protocol impact on hematopoietic stem cell collections in donors with negative collection predictors

BACKGROUND Recently, novel protocol utilizing Continuous Mononuclear Cell Collection (cMNC) have been introduced for leukapheresis. We compared the efficacy of cMNC with an older protocol - mononuclear cell collection (MNC) for CD34+ cell collection in unrelated donors with negative stem cell collection predictors. MATERIAL AND METHODS Retrospective data from a series of 258 consecutive unrelated hematopoietic stem cell donors was included in this single-center study (80 donors collected with cMNC and 178 with MNC). The donors with poor predictors for collection such as low number of circulating CD34+ cells and/or weight disproportion were assigned to the cMNC arm. RESULTS The cMNC protocol yielded a higher number of CD34 + cells per donor body weight (7.63 × 106/kg vs 6.82 × 106/kg, p = 0.027). One apheresis was sufficient for collection of target cell number in 89% individuals from both groups despite negative predictors in the cMNC group. In donors with CD34 + cell count <100/μL and a body weight disproportion between donor and recipient one apheresis was sufficient in 83% of donors in cMNC group and in 58% in MNC group (p = 0.0345) with collection efficiency CE2% values of 61% for cMNC and 62% for MNC (p = 0.77). CONCLUSION cMNC protocol is more efficient in donors with low pre-apheresis CD34+ cell count and weight disproportion between donor and recipient. This suggests that the use of cMNC in unrelated donors could possibly further improve the results of HSC collections.

Stem cell mobilization in patients with dialysis-dependent multiple myeloma: Report of the polish multiple myeloma group

High‐dose chemotherapy with autologous hematopoietic stem cell transplantation (auto‐HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto‐HSCT is also a feasible therapeutic option in MM dialysis‐dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected.

Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation

AIMS To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treatment of diabetes. METHODS APBSCT was performed in 23 patients. Control group comprised 8 non-APBSCT patients in whom after diagnosis insulin therapy was initiated. Fasting plasma glucose, glycated hemoglobin, fasting and postprandial C-peptide were assessed in all subjects and continuous glucose monitoring was performed at 6th, 12th, 24th, 36th, 48th month after transplantation. The APBSCT group was observed for 72 months. RESULTS Six months after the procedure, 22 of 23 transplant patients remained insulin-free, but after 6 years, there was only one APBSCT insulin-free patient. Good glycemic control was observed in all patients throughout the observation period, although fasting plasma glucose in control group was significantly higher in comparison with the both transplanted groups up to the 36th month. HbA1c values were significantly lower in the insulin-free group only at the 24th and 36th month. Fasting and postprandial C-peptide concentrations were higher in APBSCT group as compared with control group. The most serious adverse event was a fatal case of Pseudomonas aeruginosa sepsis. CONCLUSIONS The effectiveness of APBSCT as a treatment for newly diagnosed DM1 seems to be limited in time. The metabolic control of APBSCT patients is similar to conventionally treated patients. The lower fasting plasma glucose and higher C-peptide achieved with APBSCT seem to not exceed the risks associated with the procedure.

Biobanking of Cellular Material

Research biobanks are well-organized resources developed for the purpose of collecting, processing, storing, and distributing biological samples, accompanied by associated relevant clinical data, to make them accessible to further scientific investigation. In order to be efficient and reliable, genetic biobanks must implement specific guidelines. The detailed protocols for each step of the biobanking process strictly depend on the type and the aims of particular institution. However, some general policies should be followed, regarding key components of the banking process: obtaining informed initial consent to participate, proper collection of biological material, handling and transport of samples, freezing, storage, and retrieval of collected tissue as well as collection, protection, and sharing of relevant data.

Biobanks of Cellular Material

Cellular material can be stored for a variety of purposes, including research, diagnostics, and therapy. Common requirements are the preservation of the identity of the donor of any material, the integrity of the particular material, and informed consent from the donor for its appropriate use. The technical procedures used differ depending on whether it is necessary to preserve cell viability. When cell viability is not required, for example in typical biobanking, the requirements for the conditions of storage are less demanding. In some situations, air-dried material is sufficient, whereas in others, the material must be processed appropriately and stored frozen. The latter also applies to the storage of cellular material for future transplantation. Such material can only be stored in specialized accredited tissue establishments that must conform to prescribed quality control measures to ensure that, after thawing, the material will resume proliferative activity when transplanted.

Evaluation of relative anti-myeloma activity of high-dose melphalan followed by the first peripheral blood stem cell transplantation, as compared with the second transplantation, and to VAD chemotherapy.

Current treatment in multiple myeloma consists of three courses of chemotherapy in low doses with subsequent hematopoietic stem cell mobilization to the peripheral blood using high-dose cyclophosphamide, collection and conditioning with high-dose chemotherapy (melphalan) followed by retransplantation of autologous peripheral blood stem cells (PBSCT). Only a few studies compare the effects of different phases of therapy on parameters, such as monoclonal immunoglobulin level and the presence of malignant CD38(+) and CD56(+) cells in blood and marrow. The aim of this study was to compare the effects of these two major phases of treatment (conventional and high dose) in the same patients, and furthermore, to compare the effects of the second course of high-dose therapy followed by PBSCT with the effects of the first one. Fifteen patients were included in the study. On average, conventional chemotherapy only slightly reduced the values of all disease markers. In contrast, high-dose therapy resulted in a dramatic effect, rapidly normalizing the values of all parameters. The effects of second PBSCT were only modest compared to the first. These data suggest that high-dose therapy is an efficient method to reduce tumor load in multiple myeloma. Conventional-dose chemotherapy may be simply a waste of time for some patients and may be either omitted or administered after high-dose therapy to consolidate remission.