Search

Background Extracorporeal photopheresis (ECP) has demonstrated efficacy as second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD). The aim of our study was to analyze whether the amount of ECP-treated cells in patients with SR, aGVHD has an impact on response at 1 month. Study design and methods Data on white blood cells, lymphocytes, monocytes, mononuclear cells, and neutrophils, including absolute counts and counts per kilogram of body weight in ECP products from patients with aGVHD, were collected. For each cell population, the median dose per single ECP and the cumulative doses collected during the first week and the first month of treatment were compared with the response to ECP. Results In total, 99 patients underwent 1215 ECP procedures. Overall response was defined as a complete response if all signs of aGVHD resolved or a partial response if greater than 50% resolution was reached without other, additional immunosuppression. An overall response was obtained by 75% of patients, including 53% complete responses. Univariate analysis showed a correlation of lymphocytes and mononuclear cells/kg body weight for a single procedure and overall response. In logistic regression analysis, no tested variable had an influence on response. In receiver operating characteristic curve analysis, cutoffs of 8.4 × 106 /kg body weight lymphocytes and 13.9 × 106 /kg body weight mononuclear cells were associated with an overall response to ECP at 1 month with 75% sensitivity. Conclusion Our results in patients with steroid-refractory aGVHD confirm that response rates to ECP are high and that certain cutoff values for lymphocytes and mononuclear cells/kg body weight in each individual procedure can predict an overall response to ECP at 1 month.

BACKGROUND Peripheral blood stem cells mobilized with granulocyte–colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens. STUDY DESIGN AND METHODS We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40). RESULTS Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA–CD133+CD34+CD38low) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p

Background and Objectives Our post-thaw cell recovery rates differed substantially in interlaboratory comparisons of identical samples, potentially due to different temperatures during cell staining. Materials and Methods Viable CD34+ cells and leucocyte (WBC) subtypes were quantified by multiparameter single-platform flow cytometry in leucapheresis products collected from 30 adult lymphoma and myeloma patients, and from 10 paediatric patients. After thawing, cells were prepared for analysis within 30 min between thawing and acquisition, at either 4°C or at room temperature. Results For cell products cryopreserved in conventional freezing medium (10% final DMSO), viable cell recovery was clearly lower after staining at 4°C than at RT. Of all WBC subtypes analysed, CD4+ T cells showed the lowest median recovery of 4% (4°C) vs. 25% (RT), followed by CD3, CD34 and CD8 cells. The recovery was highest for CD3γδ cells with 44% (4°C) vs. 71% (RT). In the 10 samples cryopreserved in synthetic freezing medium (5% final DMSO), median recovery rates were 89% for viable CD34 (both at 4°C and RT) and 79% (4°C) vs 68% (RT) for WBC. Conclusions The post-thaw environment and, potentially, the cryoprotectant impact the outcome of cell enumeration, and results from the analysis tube may not be representative of the cells infused into a patient.

Background The latest technical innovation for granulocyte (PMN) collections is the fully automated Spectra Optia (Optia) device (TerumoBCT). In a retrospective investigation we evaluated the impact of the technical automation on the product quality in a routine working field. Study Design and Methods A total of 71 granulocyte collections (GCs) were collected from either routine random blood donors, mobilized with prednisolone (P; two females/23 males; median age, 42 years; range, 25-63 years), or family donors (three females/12 males; median age, 29 years; range, 21-59 years) who were mobilized with recombinant human granulocyte–colony-stimulating factor (rHuG-CSF) at a dose of 5 μg/kg body weight. All collections were performed with the Optia device. Fifty-nine concentrates (GTX) produced with the Cobe Spectra (Cobe; TerumoBCT) served as a historical control. Results In total a mean of 452 ± 60 mL with a mean purity of 83 ± 9.6% PMNs was collected with the Optia. Compared with the Cobe collections (298 ± 52 mL), the product volumes in general as well as the absolute PMN yield in P-mobilized products were significantly higher with the Optia: PMN count, 1.9 × 1010 ± 0.49 × 1010 versus 1.5 × 1010 ± 0.85 × 1010, respectively (p

Background Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative rescue therapy for patients (pts) with chemotherapy-refractory acute leukaemia. Disease control prior to HSCT is essential for long-term disease-free survival after HSCT. Patients and Methods We have retrospectively analysed the outcome of 20 pts aged 21–64 years with refractory leukaemia (acute myeloid leukaemia, n = 16; acute lymphatic leukaemia, n = 4) who received debulking therapy with clofarabine (10 mg/m², days 1–4) and cyclophosphamide (200 mg/m², days 1–4; ClofCy) prior to HSCT. Results Clofarabine/cyclophosphamide (1–4 cycles) was well tolerated and resulted in a substantial reduction of leukaemic cells in all pts. HSCT was performed in 15 of 20 pts. After HSCT (myeloablative, n = 9; dose-reduced, n = 6), all pts showed engraftment and full donor chimerism (related donors, n = 4 or unrelated donors, n = 11) and all pts achieved complete haematologic remission (CR). The median survival after HSCT is 531 days (range: 48–1462 days), and six pts are still alive after a median of 1245 days. Seven pts died after they had relapsed between days +152 and +1496. One patient died from acute graft-versus-host disease (day +48) and one from systemic fungal infection (day +87). Conclusion Clofarabine/cyclophosphamide is a novel effective treatment approach for pts with chemotherapy-refractory acute leukaemia prior to HSCT. Whether this novel debulking protocol leads to improved long-term outcome in pts with refractory leukaemias remains to be determined in forthcoming clinical studies.

Background: Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after ≥ 2 prior lines of therapy. T-cell exhaustion due to an immunosuppressive environment has been a hypothesized mechanism for CAR-T cell therapy failure. Subgroup analyses of the JULIET trial suggested an association between programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) interaction in baseline biopsies and lack of response (Agoulnik et al. EHA. 2018). Moreover, the anti-PD-1 monoclonal antibody pembrolizumab has shown clinical activity in r/r DLBCL after failing tisagenlecleucel therapy (Chong et al. Blood. 2017). PORTIA is a phase 1b, multicenter, open-label trial investigating the safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL. We report data from a completed cohort of the ongoing study. Methods: Eligible patients must be ≥ 18 years old with a confirmed diagnosis of DLBCL that has relapsed after or is refractory to ≥ 2 prior lines of therapy and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients treated with prior allogeneic stem cell transplantation, anti-CD19 therapies, or checkpoint inhibitors are excluded. Lymphodepleting chemotherapy consists of fludarabine-cyclophosphamide. Patients receive a single tisagenlecleucel intravenous infusion (target dose: 0.6-6.0x108 cells) on Day 1. Pembrolizumab is given at 200 mg every 21 days, for up to 6 doses. Pembrolizumab was started on Day 15 post-tisagenlecleucel in Cohort 1, with the option of moving to Day 8 or 22 in subsequent cohorts, based on observed data and guided by a Bayesian Logistic Regression Model with Escalation with Overdose Control principle, evaluating the distribution of dose-limiting toxicities (DLTs) occurring in the 21 days following the first pembrolizumab dose. As per study protocol, a total of 20 patients will be treated at the optimal dose timing. Primary endpoints are the proportion of patients receiving pembrolizumab per protocol schedule, the incidence of DLTs in the dose-timing selection phase, and the overall response rate in the dose-expansion phase. Secondary outcomes include duration of response, progression-free survival, overall survival, safety, cellular kinetics, and immunogenicity. Results: As of 5 March 2019, 5 patients were screened for Cohort 1. Four patients were enrolled and received tisagenlecleucel and pembrolizumab. Median age was 54 (range, 35-79). Median follow-up from time from tisagenlecleucel infusion to data cut-off was 46 days (range, 36-85). Patients received 1.7-3.0x108 CAR-positive T cells, and 1, 2, 2 and 4 pembrolizumab doses, respectively, with no delays. All 4 patients experienced at least 1 adverse event (AE), with no exacerbation or recurrence of tisagenlecleucel-related AEs following pembrolizumab infusion. No pembrolizumab-related AEs were observed. No DLTs or grade 3-4 treatment-related adverse events (TRAEs) were observed. TRAEs and AEs are summarized in Table 1. Two patients discontinued pembrolizumab treatment (after 1 and 2 doses, respectively) due to disease progression. All 4 patients experienced initial expansion between Days 6 and 15 post-tisagenlecleucel infusion, with peak transgene levels ranging from 1,980 to 77,200 copies/µg DNA (Figure 1). No secondary expansion was observed after pembrolizumab administration. The overall exposure is consistent with the observed exposure in r/r DLBCL patients in the JULIET trial. With very limited follow-up, 1 partial response has been observed. Cohort 2 (pembrolizumab starting Day 8) was ongoing at the time of submission. Conclusions: Overall, PD-1 blockade with pembrolizumab on Day 15 after tisagenlecleucel infusion was feasible and showed a manageable safety profile in the first 4 patients. No DLTs and no clinically significant exacerbation of AEs were observed, supporting the initiation of Cohort 2. Efficacy and safety data with an updated cutoff for Cohort 1 and new data from Cohort 2 will be presented at the congress. Clinical trial information: NCT03630159. Disclosures Jaeger: Novartis, Roche, Sandoz: Consultancy; AbbVie, Celgene, Gilead, Novartis, Roche, Takeda Millennium: Research Funding; Amgen, AbbVie, Celgene, Eisai, Gilead, Janssen, Novartis, Roche, Takeda Millennium, MSD, BMS, Sanofi: Honoraria; Celgene, Roche, Janssen, Gilead, Novartis, MSD, AbbVie, Sanofi: Membership on an entity's Board of Directors or advisory committees. Worel:Sanofi Genzyme, Malinckrodt Therakos: Research Funding; Jazz, Sanofi, Celgene, Novartis, Malinckrodt Therakos: Honoraria; Sanofi Genzyme, Malinckrodt Therakos: Speakers Bureau. McGuirk:Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bellicum Pharmaceuticals: Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Riedell:Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Speakers Bureau. Fleury:AstraZeneca: Consultancy; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Chu:Novartis: Employment. Abdelhady:Novartis: Employment. Forcina:Novartis: Employment. Bubuteishvili Pacaud:Novartis: Employment. Waller:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Other: Travel expenses, Research Funding; Cerus Corporation: Other: Stock, Patents & Royalties; Chimerix: Other: Stock; Cambium Oncology: Patents & Royalties: Patents, royalties or other intellectual property ; Amgen: Consultancy; Kalytera: Consultancy.

BACKGROUND: Plerixafor with granulocyte–colony-stimulating factor (G-CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty-three patients with germ cell tumor (n = 11), Ewing sarcoma (n = 6), Wiscott-Aldrich disease (n = 5), neuroblastoma (n = 4), and other nonhematologic diseases (n = 7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G-CSF (n = 21) or after chemotherapy and G-CSF (n = 12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2 × 106/kg body weight (b.w.) CD34+ cells (median, 5.0 × 106/kg b.w. CD34+ cells; range, 2.0 × 106-29.5 × 106/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5 × 106/kg b.w. CD34+ cells (range, 0.9 × 106-1.8 × 106/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3 × 106/kg b.w. (range, 2.3 × 106-6.7 × 106/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9-12) and 15 (range, 10-25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G-CSF or chemotherapy and G-CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients.

BACKGROUND: Due to the fact that the ABO and D system is inherited independently from the HLA system, approximately 40% of allogeneic hematopoietic stem cell transplants (HSCT) are performed across the blood group barrier. Reports on the development of de novo anti-D in patients undergoing reduced-intensity conditioning (RIC) followed by D-mismatched allogeneic HSCT are rare. The objective of this study was to evaluate the frequency of anti-D alloimmunization after D-mismatched HSCT following RIC and its prognostic impact on transplant outcome. STUDY DESIGN AND METHODS: Forty patients with hematologic diseases who underwent D-mismatched HSCT were retrospectively analyzed: 19 D− patients with a D+ donor and 21 D+ patients with a D− donor. Routine serologic testing for blood group typing and antibody screening was performed by a column agglutination method every time when transfusion of red blood cell units was requested and in the posttransplantation course to demonstrate establishment of donor ABO type and to detect alloimmunization. RESULTS: After a median serologic follow-up of 21 (range, 0 to 73) months after HSCT, anti-D was identified in 2 of 21 (10%) D+ patients receiving a D− transplant, 23 and 34 months after HSCT. None of the 19 D− patients with a D+ donor developed an anti-D. CONCLUSION: We observed an infrequent de novo anti-D formation that is more likely in D+ recipients of D− grafts. However, the development of anti-D does not normally impair the transplant outcome and is not of clinical relevance in the posttransplant course.

Since cytokine – mobilization for granulocyte collections in random donors – is not licensed in Austria, we investigated in a prospective analysis the effects of prednisolone or dexamethasone (DXM) in 153 donors (35 women/118 men) and in the collected products. Either prednisolone (50 mg) intravenously 4 h before granulocyte collection or DXM (8 mg) orally 12 h before collection was given. Collections were performed with the Cobe Spectra (CardianBCT, Lakewood). We recorded a significantly higher percentage of granulocytes in the peripheral blood of the DXM. However, the collected number of granulocytes was equal in both groups.

The final quality control of cryopreserved progenitor cells is a successful and persistent three lineage engraftment after transplantation. Of course, the stem cell providing institution is obliged to have a program for controlling and monitoring the manufacturing of cellular therapy products before the patients’ conditioning therapy is started. The FACT-JACIE Standards [1] and the Netcord ⁄ FACT Stan- dards prescribe that the director of the institute shall define tests and procedures for measuring and assaying cellular therapy products to ensure their safety, viability and integ- rity and shall also ensure that products meet predetermined release specifications. This requires specifications of assays and the definition of thresholds to allow release.

Background Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's disease who demonstrated with previous mobilization failure. In this named patient program we report the Austrian experience in insufficiently mobilizing patients. Study design and methods Twenty-seven patients from eight Austrian centers with a median (range) age of 58 (19-70) years (18 female, nine male) were included in the study. Plerixafor was limited to patients with previous stem cell mobilization failure and was given in the evening of Day 4 of G-CSF application. Results A median increase of circulating CD34+ cells within 10 to 11 hours from administration of plerixafor by a factor of 4.7 over baseline was noted. Overall, 20 (74%) patients reached more than 10 × 10(6) CD34+ cells/L in the peripheral blood, resulting in 17 (63%) patients collecting at least 2 × 10(6) CD34+ cells/kg body weight (b.w.; median, 2.6 × 10(6) CD34+ cells/kg b.w.; range, 0.08 × 10(6) -8.07 × 10(6) ). Adverse events of plerixafor were mild to moderate and consisted of gastrointestinal side effects and local reactions at the injection site. Thirteen (48%) patients underwent autologous transplantation receiving a median of 2.93 × 10(6) CD34+ cells/kg (range, 1.46 × 10(6) -5.6 × 10(6) ) and showed a trilinear engraftment with a median neutrophil recovery on Day 12 and a platelet recovery on Day 14. Conclusion Our study confirms previous investigations showing that plerixafor in combination with G-CSF is an effective and well-tolerated mobilization regimen with the potential of successful stem cell collection in patients with previous mobilization failure.

Background After large volume bone marrow (BM) harvest, donors and patients can develop severe anaemia, because collected BM can contain up to 20% of their red cell mass. In a prospective analysis, we investigated the feasibility to recover red blood cells (RBCs) from the harvested BM and investigated whether these RBC units meet the quality requirements of the European Council. Patients and Methods From 19 patients (median age 51 yrs, range 31–77) with acute myocardial infarction, who participated in the MYSTAR study, a median volume of 1299 ml (range, 700–1870 ml) BM was collected. During BM processing, mononuclear cells (MNC) were separated using the Cobe Spectra™ apheresis system and the residual RBCs were collected in a separate bag. The quality of the collected RBCs was assessed by measuring LDH, free haemoglobin, potassium and lactate. Haemolysis was calculated and the intracellular concentration of ATP, ADP, AMP was determined by HPLC. Results RBC units recovered from BM after MNC separation had a mean volume of 312 ± 95 ml with a haematocrit of 47 ± 8·9%, a haemoglobin content of 51 ± 15 g per unit, a haemolysis of 0·15 ± 0·005%, a pH of 6·8 ± 0·007 and an intracellular ATP concentration of 135 pmol/106 RBC ± 41, which is comparable with freshly collected packed red blood cells (PRBCs). Conclusion RBCs, collected from bone marrow harvests, can be used for autologous blood support to minimize allogeneic blood transfusions in donors and patients after large volume BM donation.

Background Recent data suggest that, among other factors, comorbidity may be an important prognostic variable in patients with myelodysplastic syndromes (MDS) who are eligible for haematopoietic stem cell transplantation (SCT). Patients and methods We examined the overall survival (OS) and underlying risk factors in 45 adult patients with MDS (n = 38), chronic myelomonocytic leukaemia (n = 1), or secondary acute myeloid leukaemia (AML) arising from MDS (n = 6), who underwent allogeneic SCT at our Institution. Results With a median follow-up of 37 months, OS for all patients was 23%, post-transplant relapse occurred in 11 patients, and 10 patients died from treatment-related complications. The overall outcome and survival was independent of cytogenetic abnormalities and International Prognostic Scoring System (IPSS). However, we identified comorbidity as defined by the haematopoietic cell transplantation specific comorbidity index (HCT-CI), as a significant adverse prognostic variable in our MDS patients. Conclusions Based on these data and similar published data we recommend selecting patients with MDS or secondary AML for SCT according to the presence of comorbidities.

OBJECTIVE. Hypermethylation of tumor suppressor genes (TSG) is thought to play an importantroleintumorigenesisofprostatecancer.Themainfocusofresearchwasthedetection ofTSGhypermethylationincancertissue.Ouraimwastoevaluatethefeasibilityofdetectionof hypermethylated genes in serum of prostate cancer patients and its correlation with clinicopathological parameters. METHODS. One hundred twenty-five serum samples from 62 patients with hormone refractory prostate cancer (HRPC), 14 patients with early disease, and 49 healthy controls were examined. After DNA extraction and sodium-bisulfite treatment, conventional methylationspecificPCR(MSP)wasperformedforglutathioneS-transferaseP1(GSTP1),androgenreceptor (AR), and 14-3-3s. RESULTS. In serum of HRCP patients, frequency of GSTP1, AR, and 14-3-3s hypermethylation was 32.2, 40.3, and 86.6%, respectively. In serum of patients with early disease frequency of GSTP1, AR, and 14-3-3s, hypermethylation was 21.4, 35.7, and 85.7%. In healthy controls, frequency of GSTP1, AR, and 14-3-3s hypermethylation was 0, 26.5, and 55.1%, respectively. There was a significant increase of frequency of TSG hypermethylation for GSTP1 and 14-3-3s in HRPC patients, in comparison with healthy controls. GSTP1 hypermethylation in HRPC patients was significantly correlated with differentiation of cancer and metastatic disease. CONCLUSIONS. Hypermethylation of TSG can be detected in serum of prostate cancer patients. Some hypermethylated TSG can be detected in serum of healthy controls. GSTP1 was not detectable in controls and correlated significantly with Gleason score and stage of disease. Therefore, this gene may be a promising new tool in prostate cancer diagnosis. Prostate # 2006 Wiley-Liss, Inc.

Background In this study, we investigated the quality of autologous mononuclear cells (MNC) collected with two different cell separators using standard MNC-apheresis procedure modalities. MNCs were purified by density gradient centrifugation and cultured according to standard protocols to generate dendritic cells (DC) and 1 × 107/ml immature DCs were pulsed with tumour lysate for 3 days and subsequently characterized by fluorescent-activated cell sorter analysis. Results No difference was found in the monocyte content of either apheresis product (P = 0·07) and in the overall yield of MNCs (P = 0·7). Mature DCs as defined by their phenotype revealed also no significant difference: Amicus‘, 118 × 106 cells ± 91 vs. AS.TEC 204®, 128 × 106 cells ± 137 (P = 0·55), respectively, although the contamination with platelets (threefold) and red cells (twofold) was significantly higher in the AS.TEC 204 group (P

BACKGROUND: ABO mismatch has not been thought to affect the outcome of patients undergoing myeloablative conditioning and allogeneic HPC transplantation. Data on transplant-related complications after ABO-mismatched transplantation after nonmyeloablative conditioning are limited. STUDY DESIGN AND METHODS: Therefore, 40 patients were analyzed after nonmyeloablative conditioning with regard to ABO compatibility. Eleven received a minor and bidirectional and 8 a major ABO-mismatched graft. RESULTS: Four patients had evidence of hemolysis during engraftment, being lethal in one, and three developed pure RBC aplasia. Six patients in the ABO-mismatched group developed thrombotic microangiopathy, and three of them died. ABO-identical and ABO-mismatched patients had a similar incidence of GVHD. Viral infections occurred in both groups in equal shares. Patients with an ABO-mismatch had to be rehospitalized until Day 100 for a median of 19 days versus 0 days in the identical group (p < 0.05). Overall survival was 60 and 57 percent in the ABO-identical and ABO-mismatch groups, respectively. The probability of transplant-related mortality was 0 versus 28 percent in the identical group compared to patients with an ABO mismatch (p < 0.05). The probability of relapse or progression was 76 versus 25 percent in the ABO-identical group compared to the ABO-mismatched group, respectively. CONCLUSION: Significantly more patients with ABO mismatch showed transplant-associated complications and died as a result of transplant-related causes.

BACKGROUND: Limited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy-induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the administration of G–CSF was compared. STUDY DESIGN AND METHODS: The study included a total of 86 patients with breast cancer (stage II-IV) receiving either CY (n = 39) or EPI-TAX (n = 47), both followed by G–CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 × 106 CD34+ cells per L of peripheral blood was reached. RESULTS: The PBPC collection was begun a median of 9 days after the administration of EPI-TAX followed by G–CSF support, as compared to a median of 13 days after mobilization with CY plus G–CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI-TAX followed by G–CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization with CY required the overall processing of 30 percent less whole-blood volume to reach the target yield of ≥10 × 106 CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G–CSF and EPI-TAX+G–CSF were equally effective in obtaining this target yield. CONCLUSION: These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.

Sepsis in profound neutropenia after chemotherapy is associated with high mortality despite appropriate antibacterial or antifungal treatment. In a prospective phase I/II study we evaluated the feasability and efficacy of leucocyte transfusions (LT) in patients with malignancies or haematological disorders who were suffering from severe bacterial or fungal infection during therapy-related bone marrow aplasia. 30 patients with severe neutropenia and clinical signs of life-threatening sepsis not responding to adequate treatment, received LT from rhG-CSF-stimulated family donors or from prednisolone-primed volunteers. A total of 301 LT were administered. The median number of LT per patient was seven (range three to 65), the median duration of LT treatment was 8 d (range 2–35). The white cell count (WBC), absolute neutrophil count (ANC) and lymphocyte count of the concentrates from rhG-CSF-stimulated donors were significantly higher than those from prednisolone-primed volunteers (P = 0.0001). Despite the critical condition of the patients, LT were generally well tolerated. Only 39 (12.9%) LT were associated with adverse reactions. The transfusion of leucocytes collected by continuous flow leukapheresis from both rhG-CSF and prednisolone stimulated donors resulted in a measurable increment of the peripheral leucocyte and ANC counts in our patients. On day 100 after the first LT, 20/30 patients were alive with complete clearance of the infection.