Impact of the number of cryopreserved CD34+ cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study.

BACKGROUND: Prospective data on the impact of CD34+ cell loss during cryopreservation and the amount of cryopreserved CD34+ cells infused after high-dose therapy on hematologic recovery and post-transplant outcome in multiple myeloma (MM) are scarce. PATIENTS AND METHODS: This post-hoc study aimed to investigate factors associating with CD34+ cell loss during cryopreservation and the effects of the infusion of a very low number (<1.0 × 106 /kg, group A), low number (1-1.9 × 106 /kg, group B), and optimal number (≥2 × 106 /kg, group C) of thawed viable CD34+ cells on hematologic recovery, progression free survival, and overall survival after autologous stem cell transplantation among 127 patients with MM. RESULTS: In group C, pegfilgrastim use (P = 0.001), plerixafor use (P = 0.039), and older age ≥ 60 years (P = 0.026) were associated with less loss of CD34+ cells during cryopreservation. Better mobilization efficacy correlated with greater CD34+ cell loss in group B (P = 0.013 and P = 0.001) and in group C (P < 0.001 and P < 0.001). Early platelet engraftment was slowest in group A (20 d vs 12 d in group B vs 11 d in group C, P = 0.003). The infused viable CD34+ cell count <1.0 × 106 /kg seemed not to have influence on PFS (P = 0.322) or OS (P = 0.378) in MM patients. CONCLUSIONS: Cryopreservation impacts significantly on the CD34+ cell loss. A very low number of graft viable CD34+ cells did not affect PFS or OS.

Efficacy of conventional-dose cytarabine, idarubicin and thioguanine versus intermediate-dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia: Long-term results of the prospective randomized nationwide AML-2003 study by the Finnish Leukemia Group.

OBJECTIVES: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy. METHODS: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively. RESULTS: A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p < .001). CONCLUSIONS: Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future.

Mobilization characteristics, blood graft composition, and outcome in diffuse large B-cell lymphoma after autologous stem cell transplantation: Results from the prospective multicenter GOA study.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common indication for autologous stem cell transplantation (auto-SCT). STUDY DESIGN AND METHODS: This prospective noninterventional study aimed to evaluate the impact of mobilization characteristics and graft cellular content on hematologic recovery and outcome after auto-SCT among 68 patients with DLBCL. RESULTS: Better mobilization capacity as manifested by blood CD34+ cell count >32 × 106 /L and CD34+ cell yield of the first apheresis >2.75 × 106 /kg correlated with faster neutrophil (P = .005 and P = .017) and platelet (P = .002 and P < .001) recovery. A higher number of infused CD34+ cells (> 2.65 × 106 /kg) was associated with better 5-year overall survival (OS; 95% vs 67%, P = .012). The graft CD34+ CD133+ CD38- cell count >0.07 × 106 /kg was predictive of better 5-year OS (87% vs 63%; P = .008) and higher graft CD3+ cell count (>23.1 × 106 /kg) correlated also with better 5-year OS (80% vs 40%, P = .008). In multivariate analysis only disease status of CR I at auto-SCT was associated with better progression-free survival (P = .014) and OS (P = .039). CONCLUSION: The mobilization capacity of CD34+ cells impacted on early hematologic recovery in patients with DLBCL after auto-SCT. Higher graft CD34+ cell count and both CD34+ CD133+ CD38- and CD3+ cells were also associated with better OS. The effect of optimal graft cellular composition on outcome in DLBCL should be evaluated in a randomized study.

Autograft cellular composition and outcome in myeloma patients: Results of the prospective multicenter GOA study.

BACKGROUND: Autologous stem cell transplantation (auto-SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known. STUDY DESIGN AND METHODS: Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study. The impact of graft cellular composition on hematologic recovery and outcome after auto-SCT was evaluated. RESULTS: A higher graft CD34+ cell content predicted faster platelet recovery after auto-SCT in both the short and long term. In patients with standard-risk cytogenetics, a higher graft CD34+ count (>2.5 × 106 /kg) was linked with shorter progression-free survival (PFS; 28 vs. 46 months, p = 0.04), but there was no difference in overall survival (OS) (p = 0.53). In a multivariate model, a higher graft CD34+ CD133+ CD38- (>0.065 × 106 /kg, p = 0.009) and NK cell count (>2.5 × 106 /kg, p = 0.026), lenalidomide maintenance and standard-risk cytogenetics predicted better PFS. In contrast, a higher CD34+ count (>2.5 × 106 /kg, p = 0.015) predicted worse PFS. A very low CD3+ cell count (≤20 × 106 /kg, p = 0.001) in the infused graft and high-risk cytogenetics remained predictive of worse OS. CONCLUSIONS: Autograft cellular composition may impact outcome in MM patients after auto-SCT. More studies are needed to define optimal graft composition.

CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non-Hodgkin's lymphoma patients: results of the prospective multicenter GOA study.

BACKGROUND: Autologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL). STUDY DESIGN AND METHODS: In this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome. RESULTS: Multiple myeloma patients mobilized CD34+ cells more effectively (6.3 × 106 /kg vs. 3.9 × 106 /kg, p = 0.001). The proportion of poor mobilizers (peak blood CD34+ cell count <20 × 106 /L) was higher in NHL patients (15% vs. 3%, p < 0.001). Plerixafor was added to rescue the mobilization failure in 17 MM patients (12%) and in 35 NHL patients (26%; p = 0.002). The infused grafts contained more natural killer (NK) and CD19+ cells in MM patients. Blood platelet and NK-cell counts were higher in MM patients posttransplant. Early treatment-related mortality was low in both groups, but NHL patients had a higher late (>100 days) nonrelapse mortality (NRM; 6% vs. 0%, p = 0.003). CONCLUSIONS: Non-Hodgkin's lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.

A prospective comparison of pegfilgrastim and lipegfilgrastim combined with chemotherapy in the mobilization of CD34+ cells in NHL patients.

BACKGROUND: Autologous stem cell transplantation (auto-SCT) is a treatment approach in non-Hodgkin lymphoma (NHL) patients. The options for mobilization of CD34+ cells to support high-dose therapy are granulocyte-colony stimulating factors (G-CSFs) alone or after chemotherapy. Limited data exist on the efficacy of lipegfilgrastim (LIPEG) in the mobilization field. PATIENTS AND METHODS: The present prospective nonrandomized study compared LIPEG 6 mg (n = 40) with pegfilgrastim (PEG) 6 mg (n = 37) in the mobilization of blood CD34+ cells after chemotherapy in NHL patients with comparable mobilizing chemotherapy and disease status before auto-SCT. RESULTS: Significantly higher blood CD34+ cell (B-CD34+ ) counts were observed in the LIPEG group at the start of the first apheresis (44 vs 23 × 106 /L, P = .009), in line with a higher collection yield of the first apheresis (3.3 vs 2.1 × 106 /kg, P = .086) and total yield of CD34+ cells (4.7 vs 2.9 × 106 /kg, P = .004). LIPEG proved to be a more effective G-CSF, resulting in a higher B-CD34+ cell peak (60 vs 32 × 106 /L, P = .030) and higher proportion of excellent mobilizers (33% vs 8%, P = .008). The superiority of LIPEG was confirmed in the multivarite analysis concerning the CD34+ cell yield of the first apheresis day (P = .010) and the total yield (P = .001). CONCLUSION: The mobilization of blood grafts with LIPEG added to chemotherapy was associated with higher CD34+ cell apheresis yields than with PEG. A randomized study is warranted to verify these findings.

Blood graft cellular composition and posttransplant outcomes in myeloma patients mobilized with or without low-dose cyclophosphamide: a randomized comparison.

BACKGROUND: Autologous stem cell transplantation is a standard treatment in multiple myeloma (MM). Blood grafts are usually collected after mobilization with granulocyte-colony-stimulating factor (G-CSF) alone or in a combination with cyclophosphamide (CY). There is limited knowledge of the possible effects of different mobilization regimens on blood graft characteristics and posttransplant outcomes. STUDY DESIGN AND METHODS: Thirty-eight patients with MM were included in this study. The patients were randomly assigned at registration to mobilization with either low-dose CY plus G-CSF (Arm A) or G-CSF alone (Arm B) and received three cycles of lenalidomide, bortetzomib, and dexamethasone induction. Flow cytometry analysis of lymphocyte subsets in the blood grafts after cryopreservation was performed. Hematologic and immune recovery were evaluated up to 12 months posttransplant. RESULTS: The blood grafts in Arm A contained significantly more CD34+ cells but in Arm B there was a greater proportion of CD34+CD38- cells and higher numbers of T and B lymphocytes as well as natural killer (NK) cells. The engraftment was comparable but lymphocyte count at 15 days posttransplant was higher in Arm B (0.8 × 10(9) /L vs. 0.5 × 10(9) /L, p = 0.033). At 3 and 6 months posttransplant the total number of NK cells was also higher in G-CSF-mobilized patients. There was no difference in progression-free survival between the study arms. CONCLUSION: CY plus G-GSF yields more CD34+ cells but seems to diminish lymphocyte and NK cell counts in the grafts and hampers immune recovery after transplantation. Thus G-CSF alone might be a preferred mobilization method due to more rapid immune recovery posttransplant.

Somatic STAT3 mutations in large granular lymphocytic leukemia.

BACKGROUND: T-cell large granular lymphocytic leukemia is a rare lymphoproliferative disorder characterized by the expansion of clonal CD3+CD8+ cytotoxic T lymphocytes (CTLs) and often associated with autoimmune disorders and immune-mediated cytopenias. METHODS: We used next-generation exome sequencing to identify somatic mutations in CTLs from an index patient with large granular lymphocytic leukemia. Targeted resequencing was performed in a well-characterized cohort of 76 patients with this disorder, characterized by clonal T-cell-receptor rearrangements and increased numbers of large granular lymphocytes. RESULTS: Mutations in the signal transducer and activator of transcription 3 gene (STAT3) were found in 31 of 77 patients (40%) with large granular lymphocytic leukemia. Among these 31 patients, recurrent mutational hot spots included Y640F in 13 (17%), D661V in 7 (9%), D661Y in 7 (9%), and N647I in 3 (4%). All mutations were located in exon 21, encoding the Src homology 2 (SH2) domain, which mediates the dimerization and activation of STAT protein. The amino acid changes resulted in a more hydrophobic protein surface and were associated with phosphorylation of STAT3 and its localization in the nucleus. In vitro functional studies showed that the Y640F and D661V mutations increased the transcriptional activity of STAT3. In the affected patients, downstream target genes of the STAT3 pathway (IFNGR2, BCL2L1, and JAK2) were up-regulated. Patients with STAT3 mutations presented more often with neutropenia and rheumatoid arthritis than did patients without these mutations. CONCLUSIONS: The SH2 dimerization and activation domain of STAT3 is frequently mutated in patients with large granular lymphocytic leukemia; these findings suggest that aberrant STAT3 signaling underlies the pathogenesis of this disease. (Funded by the Academy of Finland and others.).

Blood graft cellular composition and posttransplant recovery in non-Hodgkin's lymphoma patients mobilized with or without plerixafor: a prospective comparison.

BACKGROUND: Autologous stem cell transplantation is commonly used to treat non-Hodgkin's lymphomas (NHLs). Cellular composition of the blood grafts apparently has a role in the posttransplant hematologic and immune recovery. Plerixafor increases the mobilization of CD34+ cells and higher amounts of various lymphocyte subsets have been reported in the grafts. Limited prospective data are available in regard to graft cellular composition, hematologic and immune recovery, and patient outcomes in NHL patients who receive plerixafor added to chemomobilization. STUDY DESIGN AND METHODS: Forty-one patients with NHL participated in this prospective study. All patients received chemomobilization and 15 poor mobilizers also received plerixafor. CD34+ cell subsets and lymphocyte subsets of cell grafts, posttransplant hematologic and immune recovery, and outcome were evaluated. RESULTS: Blood grafts in the plerixafor group contained a significantly higher proportion of CD34+133+CD38- cells and more lymphocytes of all major subsets except B lymphocytes. Neutrophil engraftment was comparable and platelet recovery slightly slower in the plerixafor group. Natural killer cell recovery was significantly faster in patients mobilized with plerixafor. Otherwise hematologic and immune recovery as well as short-time outcome were comparable even though there was a trend for progression-free survival and overall survival benefit in the plerixafor group. CONCLUSIONS: In poorly mobilizing NHL patients, plerixafor added to chemomobilization is safe and effective. It also modifies the blood graft composition in many ways, some of which have been linked to better outcomes in previous studies. Larger sets of patients and longer follow-up are needed to see whether plerixafor-mobilized grafts are associated with superior outcome of the patients.

Engraftment and outcome after autologous stem cell transplantation in plerixafor-mobilized non-Hodgkin's lymphoma patients.

BACKGROUND: Plerixafor is used in combination with granulocyte-colony-stimulating factor to enhance the mobilization of hematopoietic stem cells. Limited data are available in regard to effects of plerixafor on posttransplant outcomes in chemomobilized patients who appear to mobilize poorly. STUDY DESIGN AND METHODS: Eighty-nine chemomobilized patients with non-Hodgkin's lymphoma (NHL) were included in this retrospective study. Thirty-three patients had received plerixafor preemptively (plerixafor group) and 56 patients served as controls. Posttransplantation outcomes including infections, hematologic recovery, and relapse were recorded. RESULTS: The median fold increase of CD34+ cells after the first plerixafor dose was 4.1 in patients mobilized with chemotherapy plus filgrastim and 7.2 in those mobilized with chemotherapy plus pegfilgrastim (p = 0.027). The median number of collected CD34+ cells was 3.5 × 10(6) CD34+ cells/kg in the plerixafor group and 4.2 × 10(6) CD34+ cells/kg in the control group (p = 0.076). Early engraftment was comparable between the groups (10 days for neutrophils >0.5 × 10(9) /L and 14 days for platelets >20 × 10(9) /L, respectively). Also late engraftment within 12 months was comparable except higher hemoglobin level at 3 months in the control group (121 g/L vs. 112 g/L, p = 0.009). Progression-free survival at 1 year after autologous stem cell transplantation (ASCT) was 79% in the plerixafor group and 86% in the control group (p = 0.399). CONCLUSIONS: Long-term engraftment and outcome after ASCT seem to be comparable in NHL patients receiving plerixafor compared to chemomobilized patients. These observations support the use of plerixafor in patients who mobilize poorly.

CD34+ cell subclasses and lymphocyte subsets in blood grafts collected after various mobilization methods in myeloma patients.

BACKGROUND: Cyclophosphamide (CY) combined with granulocyte-colony-stimulating factor (G-CSF) is commonly used to mobilize stem cells in multiple myeloma (MM). Plerixafor may also be used with G-CSF in patients who mobilize poorly or it may be added to chemomobilization to boost mobilization. Limited data are available on graft content collected after various mobilization methods. STUDY DESIGN AND METHODS: Blood grafts collected from 21 MM patients were retrospectively analyzed. We analyzed CD34+ subclasses and lymphocyte subsets from cryopreserved grafts collected on the next morning after plerixafor injection in nine MM patients mobilized with G-CSF with (n = 5) or without preceding CY (n = 4). As controls we had the first collections from 12 MM patients mobilized with low-dose CY with G-CSF. RESULTS: The proportion of the most primitive stem cells (CD34+CD133+CD38-) from all CD34+ cells in the graft was higher in the plerixafor-treated patients but there was no significant difference in the total number of these cells. The numbers of CD19+ B lymphocytes and natural killer cells were higher in patients collected after G-CSF plus plerixafor when compared to the patients mobilized with CY plus G-CSF. Early engraftment after high-dose melphalan was comparable between the groups. CONCLUSION: Plerixafor appears to have effects on blood stem cell graft composition in myeloma patients. A higher number of grafts should be evaluated in regard to cellular content and longer follow-up of the patients is needed to evaluate the potential clinical impact of graft content.

Loss of CD34+ Cells and Effect of the Number of Viable Cryopreserved CD34+ Cells in the Infused Blood Grafts on Hematologic Recovery, Progression-Free Survival and Overall Survival in NHL Patients After Autologous Stem Cell Transplantation.

PATIENTS: This post-hoc study aimed to find out factors affecting graft viable CD34+ cell loss during processing and cryopreservation in 129 non-Hodgkin lymphoma (NHL) patients receiving autologous stem cell transplantation (auto-SCT) and the impact of a low (< 2.0 × 106/kg, group A) and a decent number (≥ 2 × 106/kg, group B) of viable CD34+ cells infused on the hematologic recovery, progression-free survival (PFS) and overall survival (OS) after auto-SCT. RESULTS: The median loss of viable CD34+ cells during cryopreservation was higher in group A (47% vs. 19%, p < .001). A higher yield of CD34+ cells at the first apheresis in group B (p = .002) was linked with greater loss of viable graft CD34+ cells after cryopreservation. Filgrastim (FIL) use for mobilization seemed to associate with higher viable CD34+ cell loss compared to pegfilgrastim (PEG) or lipegfilgrastim (LIPEG) in both groups (in group A FIL 66 vs. PEG 35%, p = .006; in group B FIL 37 vs. PEG 15 vs. LIPEG 13%, p < .001). Hematologic recovery after auto-SCT was faster in group B. Neither viable CD34+ cell loss during storage nor viable CD34+ cell number < 2.0 × 106/kg infused affected on PFS or OS. CONCLUSIONS: G-CSF type used in mobilization and mobilization capacity were found to correlate with viable CD34+ cell loss during processing and storage. Most importantly, low infused viable CD34+ cell count did not seem to impact on PFS or OS.

Blood graft lymphocyte subsets after plerixafor injection in non-Hodgkin's lymphoma patients mobilizing poorly with chemotherapy plus granulocyte-colony-stimulating factor.

BACKGROUND: A combination of chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) (chemomobilization) is commonly used to mobilize CD34+ cells to circulation. Plerixafor, a chemokine CXCR4 antagonist, increases the mobilization of CD34+ cells and may also have effect on graft composition. STUDY DESIGN AND METHODS: We have analyzed lymphocyte subsets in grafts collected on the next morning after plerixafor injection in 13 chemomobilized patients with non-Hodgkin's lymphoma (NHL) mobilizing poorly. As controls we had the first leukapheresis products from 11 NHL patients mobilized with chemotherapy plus G-CSF. The analyses were performed from cryopreserved apheresis products. RESULTS: The median counts of both total CD3+ T cells and natural killer (NK) cells (CD3-CD16/56+) in the graft were significantly higher in plerixafor-treated group compared to the control group. Both helper T-lymphocytes (CD3+CD4+) and suppressor T-lymphocytes (CD3+CD8+) were significantly increased in the plerixafor-treated group so that CD4+/CD8+ ratio in the graft did not differ between the groups. CD19+ cells were evident only at very small amounts in few patients in both groups, and the CD34+ cell content of the graft did not differ between the groups. Engraftment after high-dose therapy was comparable between the groups. CONCLUSION: Plerixafor added to chemomobilization in poor mobilizers seems to mobilize more T cells and NK cells than chemomobilization. Larger patient numbers and longer follow-up is needed in regard to evaluate posttransplant complications and risk of relapse in patients receiving plerixafor due to poor mobilization.

Blood graft composition after plerixafor injection in patients with NHL.

BACKGROUND: Plerixafor is used to mobilize CD34(+) hematopoietic stem cells from bone marrow to circulation. Limited data are available in regard to graft cellular content collected after plerixafor. OBJECTIVES: The aim of this study was to assess effects of plerixafor added to chemomobilization on graft CD34(+) cell subclasses, lymphocyte subsets, engraftment, and post-transplant course in non-Hodgkin lymphoma (NHL) patients. METHODS: Thirty-four patients with NHL were included. All patients received chemotherapy plus G-CSF to mobilize stem cells. Nineteen patients received plerixafor pre-emptively owing to poor mobilization or poor collection yields. The rest of the patients constituted the control group. Flow cytometric analyzes were performed from cryopreserved graft samples. Also, data on post-transplant engraftment and outcome were collected. RESULTS: The proportion of primitive stem cells (CD34(+)  CD133(+)  CD38(-) ) was significantly higher after the plerixafor injection when compared to the first collection in the control group. The amount of T cells (CD3(+) ), helper (CD3(+)  CD4(+) ) T subsets, and suppressor (CD3(+)  CD8(+) ) T subsets in the graft was all significantly higher in the plerixafor group. Also, the amount of NK cells (CD3(-)  CD16/56(+) ) was higher. Engraftment after high-dose therapy was comparable between the groups, but leukocyte and platelet count at 6 months were higher in patients receiving plerixafor-mobilized grafts. CONCLUSION: Plerixafor, when used pre-emptively in addition to chemomobilization, seems to mobilize more primitive CD34(+) stem cells, T lymphocytes, and NK cells. Whether these differences are associated with immune reconstitution, long-term engraftment, or patient outcomes needs to be evaluated in larger patient groups with longer follow-up.

Serum cortisol and inflammatory response in neutropenic fever.

There are no data on serum cortisol of hematological patients at the onset of neutropenic fever and its possible association with the severity of infection. The purpose of this study was to evaluate the association of serum cortisol with the level of C-reactive protein (CRP) and procalcitonin (PCT), widely used markers of infection and inflammation, and with the development of severe sepsis in this patient group. All clinical data were collected prospectively at the hematology ward of Kuopio University Hospital. Altogether, 69 hematological patients with 93 periods of neutropenic fever were included. Nineteen patients received therapy for acute myeloid leukemia, and 50 patients were autologous stem cell transplantation recipients. Each period of neutropenic fever was classified as severe sepsis or not. Serum cortisol, CRP, and PCT were determined at the onset of fever on day 0 and then at 8-9 a.m. on days 1-4. Level of serum cortisol correlated positively with maximal CRP level during days 0 to 4 in neutropenic fever periods without severe sepsis, but no correlation was observed in fever periods with severe sepsis. To conclude, the level of cortisol correlated with the severity of infection measured as maximal CRP or elevated PCT in fever periods without severe sepsis, but in fever periods with severe sepsis, the cortisol response was attenuated.

Efficacy of pre-emptively used plerixafor in patients mobilizing poorly after chemomobilization: a single centre experience.

A significant proportion of patients with lymphoid malignancies are hard-to-mobilize with a combination of chemotherapy plus granulocyte colony-stimulating factor (G-CSF) (chemomobilization). Plerixafor is a novel drug used to improve mobilization of blood stem cells. However, it has been studied mainly in association with G-CSF mobilization. We evaluated the efficacy of 'pre-emptive' use of plerixafor after chemomobilization in patients who seem to mobilize poorly. During a 15 month period, altogether 63 patients with lymphoid malignancies were admitted to our department for blood stem cell collection. Sixteen patients (25%) received plerixafor after the first mobilization due to the low blood (B) CD34(+) cell counts (n = 12) or poor yield of the first collection (n = 4). The median number of plerixafor injections was 1 (1-3). The median B-CD34(+) count after the first plerixafor dose was 39 × 10(6) /L (<1-81) with the median increase of fivefold. Stem cell aphaereses were performed in 14/16 patients (88%) receiving plerixafor and a median of 2.9 × 10(6) /kg (1.6-6.1) CD34(+) cells were collected with a median of one aphaeresis (1-3). Altogether 13/16 patients mobilized with a combination of chemomobilization and plerixafor received high-dose therapy with stem cell support and all engrafted. Pre-emptive use of plerixafor after chemomobilization is efficient and safe and should be considered in poor mobilizers to avoid collection failure. In patients with low but rising B-CD34(+) counts, the use of plerixafor might be delayed as late mobilization may occur. Further studies are needed to optimize patient selection and timing of plerixafor.

Elevated procalcitonin predicts Gram-negative sepsis in haematological patients with febrile neutropenia.

OBJECTIVE: To compare semi-quantitative procalcitonin with C-reactive protein in predicting bacteraemia in haematological patients with neutropenic fever. METHODS: A total of 77 patients treated with intensive chemotherapy for haematological malignancy at Kuopio University Hospital were candidates for study entry. Eleven of these patients did not fulfil the criteria for neutropenic fever, and 66 patients were finally included. Nineteen patients had acute myeloid leukaemia and 47 had received high-dose chemotherapy supported by autologous stem cell transplant. Ninety neutropenic fever episodes in these 66 patients fulfilled the study entry criteria, with microbiological cultures, procalcitonin and C-reactive protein measurements available. Serum procalcitonin and C-reactive protein were analyzed at the onset of each neutropenic fever episode on day 0, and then daily from days 1 to 4. RESULTS: Bacteraemia was observed in 21 episodes (23%) and the criteria for severe sepsis were fulfilled in 13 episodes (14%). Half of the bacteraemic episodes were caused by Gram-negative bacteria. The kinetics of procalcitonin and C-reactive protein were similar, with increasing levels for 2 to 4 days after the onset of fever. The procalcitonin level on days 1, 2, 3 and 4 was associated with bacteraemia and Gram-negative bacteraemia, but not with the development of severe sepsis. On day 1, a procalcitonin level above 0.5 ng/ml had a sensitivity of 57% and 70% and specificity of 81% and 77% to predict bacteraemia and Gram-negative bacteraemia, respectively. CONCLUSIONS: An elevated level of procalcitonin within 24 h after the onset of neutropenic fever predicts bacteraemia and Gram-negative bacteraemia in haematological patients.

Blood Graft and Outcome After Autologous Stem Cell Transplantation in Patients With Primary Central Nervous System Lymphoma.

BACKGROUND: Autologous stem cell transplantation (auto-SCT) is a treatment option for patients with primary central nervous system lymphoma (PCNSL). METHODS: In this prospective multicenter study, the effects of blood graft cellular content on hematologic recovery and outcome were analyzed in 17 PCNSL patients receiving auto-SCT upfront. RESULTS: The infused viable CD34+ cell count > 1.7 × 106/kg correlated with more rapid platelet engraftment (10 vs. 31 days, P = 0.027) and with early neutrophil recovery (day + 15) (5.4 vs. 1.6 × 109/L, P = 0.047). A higher number of total collected CD34+ cells > 3.3 × 106/kg infused predicted worse 5-year progression-free survival (PFS) (33% vs. 100%, P = 0.028). In addition, CD3+CD8+ T cells > 78 × 106/kg in the infused graft impacted negatively on the 5-year PFS (0% vs. 88%, P = 0.016). CONCLUSION: The cellular composition of infused graft seems to impact on the hematologic recovery and PFS post-transplant. Further studies are needed to verify the optimal autograft cellular content in PCNSL.

Serial plasma lactate measurements in haematological patients with neutropenic fever.

Elevated plasma lactate and impaired lactate clearance have been associated with poor outcome in patients with severe sepsis. No data are available on the kinetics or prognostic value of plasma lactate in haematological patients with neutropenic fever. A total of 70 haematological patients with 94 episodes of neutropenic fever were included into this prospective study during the period 2006-2008. The median age of the patients was 56 (range 18-70) y. Nineteen patients received therapy for acute myeloid leukaemia and 51 patients received autologous stem cell transplantation. At the onset and on days 1, 2, and 3 of each neutropenic fever episode, plasma lactate and serum C-reactive protein were determined. Criteria for severe sepsis were fulfilled in 13 neutropenic episodes. An elevated plasma lactate level was infrequent at the start of neutropenic fever (5%). There was no association of lactate level with the development of severe sepsis. Two patients died of septic shock, 1 patient with an exceptionally high and increasing level of lactate and the other patient with a normal lactate level. An elevated plasma lactate level at the start of neutropenic fever is not common and does not indicate severe sepsis, but high lactate and an impaired lactate decrease may signify a fatal course in neutropenic fever.

Autograft cellular composition and outcome in NHL patients: results of the prospective multicenter GOA study.

Autologous stem cell transplantation (auto-SCT) is an established treatment option in patients with non-Hodgkin lymphoma (NHL). In this prospective multicenter study, the effect of infused blood graft cellular composition on post-transplant outcome was analyzed in 129 NHL patients. Higher graft CD34+ cell content (>2.5 × 106/kg) correlated with better progression-free survival (PFS) (p=.009) and overall survival (OS) (p=.004). Higher graft CD34+CD133+CD38- counts (>0.08 × 106/kg) were also linked with better PFS (p=.03) and OS (p=.004), and these survival benefits retained in multivariate analyses. Higher infused CD3+CD4+ cell count (>37 × 106/kg) predicted better PFS (p=.013) and OS (p=.007) in multivariate analysis. Autograft cellular composition seems to impact outcome in NHL patients. These observations regarding composition of optimal graft in autologous setting should be validated in an independent patient series or in a randomized study.