High White Blood Cell Concentration in the Peripheral Blood Stem Cell Product Can Induce Seizures during Infusion of Autologous Peripheral Blood Stem Cells

Seizures as a complication of the infusion of autologous peripheral blood stem cells (PBSC) are rare. Seizures during infusion of autologous PBSC in 3 of our patients prompted us to review our cell therapy and cytapheresis protocols and procedures. We retrospectively analyzed 159 adult patients collected between January 2006 and July 2009. Patients were collected on either the COBE Spectra (Caridian BCT, Lakewood, CO) cell separator (n = 85) or Fresenius AS (Fresenius Kabi AG, Bad Homburg, Germany) 104 cell separator (n = 74) and mobilized with granulocyte-colony stimulating factor (G-CSF) alone (n = 47), G-CSF and Plerixafor (n = 36), or G-CSF and chemotherapy (n = 76). Patient characteristics (including age, weight, number of collections, volume processed, disease type, and mobilization strategy) did not differ significantly between the COBE and Fresenius cohorts, and adverse effects from infusion were similar except for 3 of 159 patients who experienced seizures upon infusion of PBSC; all 3 were collected on the COBE and had PBSC product white blood cell (WBC) counts of 590 × 103/μL or above. We prospectively correlated WBC counts midcollection, with final WBC counts to identify products with high WBC concentration during cytapheresis. Fifty-one patients had 66 cytapheresis procedures using the COBE, with WBC counts midway and at the end of collection of 287 × 103 ± 150/μL and 273 × 103 ± 144/μL, respectively. Mid-WBC therefore correlated with WBC at the end of the collection. Finally, we prospectively collected mid-WBC from 65 patients who underwent 80 PBSC collections between June 2009 and January 2010 to identify products with midcollection WBC concentration >450 × 103/μL. In those cases, additional autologous plasma was collected at the time of collection to dilute the final product before cryopreservation. Patients who received diluted products experienced no delays in engraftment and no additional seizure episodes occurred

2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants

Digitalitzat per Artypla

Long-Term Follow-Up of Patients Who Experienced Graft Failure Postallogeneic Progenitor Cell Transplantation. Results of a Single Institution Analysis

AbstractThe long-term outcome of graft failure after allogeneic stem cell transplantation (SCT) has not been well described. To fill this knowledge gap we performed a retrospective analysis of patients with graft failure over a 10-year time period in a single institution. Cases were included for analysis if they had failed to achieve an absolute neutrophil count (ANC) of 500/μL or more by 28 days post-SCT or 42 days after cord blood transplantation (primary graft failure); had a decrease in their ANC to <500/mL for 3 consecutive days after having achieved neutrophil engraftment (secondary graft failure); or failed to have evidence of at least 5% or more donor cell engraftment (primary graft failure with autologous reconstitution). Among 1726 patients who underwent allografts from January 1, 1990, through December 31, 2000, we identified 68 patients with graft failure. The 1-, 2-, and 5-year overall survival (OS) for all patients was 31%, 24%, and 15%. A diagnosis of acute leukemia was a significant predictor for poor survival on multivariate analysis. We conclude that graft failure is an uncommon complication postallogeneic SCT, and is associated with poor outcomes. Collection of autologous stem cells prior to high-risk allografting can salvage a fraction of patients and lead to prolonged survivals

Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia

Allogeneic stem cell transplantation is the only curative option for patients with hereditary bone marrow failure syndromes. Umbilical cord blood is an alternative source of stem cells for allogeneic transplantation

Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia

O transplante com células tronco hematopeticas é a única opção curativa para os pacientes com síndromes de insuficiência medular hereditárias (SIMH). O sangue de cordão umbilical é uma fonte alternativa de células tronco hematopoéticas para o transplante alogênico. Pacientes e métodos: Este estudo retrospectivo e multicêntrico é baseado em dados do registro Eurocord sobre pacientes com SIMH, excluindo os paciente com anemia de Fanconi, que receberam transplante de sangue de cordão umbilical (TCU). Resultados: Sessenta e quatro pacientes com SIMH foram transplantados com doador aparentado (n=20) e não aparentado (n=44). Os diagnósticos foram: anemia de Blackfan Diamond (21 pacientes), trombocitopenia amegacariocítica congênita (16 pacientes), disqueratose congênita (8 pacientes), síndrome de Shwachman-Diamond (2 pacientes), neutropenia congênita grave (16 pacientes) e SIMH inclassificável (1 paciente). No grupo aparentado, 19 pacientes receberam transplante HLA compatível do irmão. A mediana de células nucleadas totais (CNT) infundidas foi 5x107/kg. A incidência cumulativa da recuperação de neutrófilos em 60 dias foi 95%, 2 pacientes tiveram doença do enxerto contra hospedeiro (DECH) grau II a IV e a incidência cumulativa em 2 anos de DECH crônica foi 11%. A sobrevida global (SG) em 3 anos foi 95%. No grupo não aparentado, 86% dos pacientes receberam enxerto com incompatibilidade HLA e 3 receberam duas unidades de cordão umbilical. A mediana de CNT infundidas foi 6,1x107/kg. A incidência cumulativa da recuperação de neutrófilos em 60 dias foi 55%; de DECH grau II a IV em 100 dias foi 24% e de DECH crônica em 2 anos foi 53%. A SG em 3 anos foi 61%; melhor SG foi associada com idade < 5 anos (p=0,01) e número CNT infundidas ? 6.1x107/kg (p=0,03). Conclusão: em pacientes com SIMH, TCU aparentado é associado com excelentes resultados enquanto no TCU não aparentado o aumento no número de células promove melhoresresultadosBackground: Allogeneic stem cell transplantation is the only curative option for patients with hereditary bone marrow failure syndromes (HBMFS). Umbilical cord blood (UCB) cells is an alternative stem cell source for allotransplantation. Design and Methods: This multicenter, retrospective study is based on data reported to Eurocord Registry about patients with HBMFS other than Fanconi anemia who received UCB transplantation (UCBT). Results: Sixty four patients with HBMFS were transplanted from related (n=20) or unrelated donors (n=44). Diagnoses were: Diamond-Blackfan anemia (21 patients), congenital amegakaryocytic thrombocytopenia (16 patients), dyskeratosis congenita (8 patients), Shwachman-Diamond syndrome (2 patients), severe congenital neutropenia (16 patients) and unclassified HBMFS (1 patient). In the related group, all patients but one received an HLA-matched sibling transplant. Median total nucleated cells (TNC) infused was 5x107/kg. Cumulative incidence (CI) of 60-day neutrophil recovery was 95%, 2 patients had grade II-IV acute graft-versus-host disease (GVHD), while the 3-year CI of chronic GVHD was 11%. The 3-year overall survival (OS) was 95%. In the unrelated group, 86% of patients had HLA mismatched grafts and 3 received two UCB units. Median TNC infused was 6.1x107/kg. Day-60 CI of neutrophil recovery was 55%; 100-day CI of grade II-IV acute GVHD was 24%, while 2-year CI of chronic GVHD was 53%. The 3-year OS was 61%; better OS was associated with age < 5 years (p=0.01) and a number of TNC infused ? 6.1x107/kg (p=0.03). Conclusion: in patients with HBMFS, related UCBT is associated with excellent outcomes while in unrelated UCBT increasing cell dose might provide better result

Donor-Recipient Host-Versus-Graft (HVG) HLA Mismatches and Outcome of Cord Blood Transplants (CBT)

Abstract The influence of HLA mismatches on outcomes of CBT is yet to be fully defined. We hypothesized that donor-recipient mismatches in the host-versus-graft (HVG) and graft-versus-host (GVH) direction impact engraftment, treatment-related mortality (TRM) and survival after CBT, and addressed the question studying CBT performed in our institution from 3/1996 to June/2006. Methods: 91 patients (pts) were analyzed. Diagnoses were high-risk hematologic malignancies (n=85; 93%) or non-malignant disorders (n=6; 7%). Conditioning was myeloablative (n=86; 95%), while patients not eligible for high-dose therapy received reduced-intensity (n=5; 5%) regimens. ATG was part of the preparative regimen in 45 cases (49%). GVHD prophylaxis was tacrolimus with (n=83; 91%) or without methotrexate (n=6; 6%), and cyclosporine and MMF (n=2; 2%). Grafts were single (n=70; 77%) or double (n=21; 23%) CB units. 9 pts received ex-vivo expanded grafts. For patients receiving a double CBT, the engrafted unit was used as the reference for this analysis. HLA-A, B (intermediate resolution) and DRB1 typing (high-resolution) was available for all donor-recipient pairs. Results: Median age was 18 years (1–57); 46 (51%) were younger than 18 yrs old and 50 pts (55%) were males. The patients were heavily pre-treated with 18 (20%) having received prior autotransplants. Disease status at CBT was complete remission (CR; n=43; 47%) and active disease (n=48; 53%). Median number of infused total nucleated cell was 3.45x10E7/kg (0.81–23.6). Numbers of mismatches in the HVG direction were as follows: zero (n=11), 1 (n=37), 2 (n=36), 3 (n=6), and 4 (n=1). Numbers of mismatches in the GVH direction were as follows: zero (n=8), 1 (n=35), 2 (n=41), and 3 (n=7). 78 pts engrafted neutrophils (86%) at a median of 22 days (4–60). 65 pts engrafted platelets (71%) at a median of 42 days(0–133). 13 pts (14%) failed to engraft. Grade II–IV and III–IV acute GVHD rates were 49% and 8%, respectively, and chronic GVHD incidence was 33%. 35 pts are alive with a median follow-up of 25 months. 2-yr actuarial survival is 21%. 100-day and 1-yr NRM is 22%(14–32) and 37% (28–49). The influence of HVG mismatches on NRM, survival and engraftment is shown in the table and figure. The decreasing 2-yr survival and worse NRM associated with increasing number of HVG mismatches was limited to the group of pts <18 yrs old. There was no difference in the proportion of pts in CR, nor in the distribution of infused TNC/Kg across the HVG mismatch subgroups. There was no correlation between mismatches in the GVH direction and NRM or 2-yr survival. Conclusion: HVG mismatches may influence outcomes of CBT. Number of Mismatches - HVG direction 1-yr NRM % engrafted Abbreviations: HVG: host-versus-graft; NRM: non-relapse mortality; NS: not significant 0 n=11 21% (CI: 6–74) 100 1 n=36 33% (CI: 20–54) 89 2 n=34 47% (CI: 33–67) 85 3 n=6 33% (CI: 11–100) P=NS 83 Figure Figur