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Patients with amyotrophic lateral sclerosis (ALS) experience progressive and irreversible paralysis as a result of the continued loss of motor neurons, which leads to death in less than five years. To date, there is no treatment that can change the progression of this disease. Bone marrow stem cells have shown neural regenerative and neural repairing properties. Specifically, our group showed in a murine model of the disease that these cells, when injected in the spinal cord, can rescue motor neurons through the secretion of GDNF. Based on these results, we designed a phase I/II clinical trial for the purpose of demonstrating the viability of the intraspinal injection of autologous bone marrow mononuclear cells in patients with bulbar onset ALS, with an evolution between 6 and 36 months, with a forced vital capacity (FVC) 50% and T90 29%. This article describes the technique for extracting 60 mL of bone marrow used for the intervention, processing it by density gradient, and the neurosurgical technique used for implanting it. After 6 months of follow-up, the few adverse events reported in the first seven patients included seem to show that the procedure is safe and viable. Most of these patients, including two with a rapid deterioration, have stabilized the progression of their FVC and the neurologic scales measured. The data obtained so for seem to justify the design of new trials more oriented toward the efficacy of the procedure.

We have analysed two Caucasian families in which recombinant individuals have been identified. In both families, initial low resolution typing of class I and II antigens of possible patients referred for bone marrow transplantation and their respective potential donors (based on inherited haplotypes analysis) revealed them to be HLA identical and supposedly inheriting-non-recombinant haplotypes. The mothers were found to be DRB1*04 generic allele homozygous, but possessing two DRB1*04 specific alleles, DRB1*0403 and DRB1*0404 (family A) and DRB1*0401 and DRB1*0402 (family B). In both cases the patients inherited a maternal haplotype that is the result of a recombination event between the mother's HLA-DRB1 and -B genes on their chromosomes. Based on linkage disequilibrium it is likely that the recombinant haplotypes are present in the patients rather than their brothers. In both families, the results of the MLC in terms of relative response was positive. Thus, these cases illustrate the importance of high resolution DNA class II typing when assignment of MHC antigens is of extreme importance (i.e. bone marrow transplantation).

We retrospectively compared the incidence and clinical characteristics of cGVHD in 37 allo-PBT recipients transplanted between July 1994 and October 1996 and 37 historical control allo-BMT recipients in a case-control study. All patients received a first unmanipulated transplant, graft from an HLA-identical sibling donor, with CsA-MTX GVHD prophylaxis and survived more than 100 days after transplant. PBT and BMT groups were well matched for age, grade of acute GVHD, male patients grafted from female donors, and phase of disease. The median CD34+ and CD3+ cell numbers infused in the PBT group were 5.2 x 10(6)/kg and 307 x 10(6)/kg, respectively. The median time to an ANC greater than 0.5 x 10(9)/l was 16 days (range 11-22) after PBT and 22 days (range 14-36) after BMT (P < 0.001). The median time to a platelet count greater than 20 x 10(9)/l was 15 days (range 6-43) after PBT and 28 days (range 12-68) after BMT (P < 0.001). Median follow-up was 12.3 months (range 5.4-30.3) and 58.7 months (range 4-122.3), for patients receiving PBT and BMT, respectively. Seventeen out of 37 (46%) PBT recipients, vs nine out of 37 (24%) BM recipients developed cGVHD. Actuarial probability of cGVHD at 1 year was 59% (95% CI, 39-79) in the PBT group vs 27% (95% CI, 12-42) in the BM group (P = 0.01). Cumulative incidence estimate of cGVHD was 51% and 25%, for patients receiving PBT and BMT respectively (P = 0.03). Clinical characteristics of cGVHD and response to therapy were similar in both groups, except for a higher incidence of de novo cGVHD in the PBT group. Our results suggest that as compared with BMT, PBT may result in an increased incidence of cGVHD.

We performed a prospective study in 17 consecutive patients following Autologous bone marrow (BM) or rhG-CSF primed peripheral blood item cell (PBSC) transplantation, with the objective of comparing immune recovery between both procedures and to evaluate results in rhG-CSF mobilized peripheral blood stem cell transplantation (PBSCT). Kinetics of immune reconstitution showed differences, with a faster recovery of CD3+ and CD8+ T cells, and a more rapid and sustained recovery of CD8+/-/CD56+ natural killer (NK) cells in the PBCSCT group. Autologous bone marrow transplantation (ABMT) was associated with a improved reconstitution of the CD19+/CD5+/-subpopulation. Moreover, rhG-CSF mobilized PBSCT generated a greater recovery of CD8+/-/CD56+ cells than previous data concerning transplantation with peripheral blood (PB) progenitors collected after myelosuppressive chemotherapy or myelosuppressive therapy plus rhG-CSF. Our results show differences in the rate and pattern of B and T lymphocytes reconstitution after ABMT and PBSCT. Additionally, we state an enhancement of CD56+ cells in patients undergoing PBSCT mobilized solely using rhG-CSF.

Background: A comparative analysis of the economic costs of the different methods of autologous transplantation was carried out., Methods: A series of 22 patients was retrospectively studied: 8 treated with autologous bone marrow transplantation (ABMT), 9 treated with peripheral blood stem cell (PBSC) transplantation and 5 in whom mixed transplantation of bone marrow and peripheral blood hematopoietic progenitors was performed. The expenses derived from pretransplant studies and from the collection of hematopoietic progenitors and from the autologous transplantation procedure itself were evaluated., Results: The pretrasplant study and the collection of hemopoietic progenitors were significantly more expensive in the PBSC than in the ABMT (p = 0.04 and p = 0.007, respectively). Nonetheless, the costs of the transplant procedure were lower in the PBSC than in the ABMT group although the differences were not statistically significant. The estimated costs of these procedures in the Hematology Unit of the General Hospital of the University of Murcia, Spain, is of 3 million pesetas for the ABMT and 2.5 million for the PBSC. The greatest cost observed in the ABMT was due to these patients requiring longer hospitalization, greater transfusion support and longer antibiotic treatment., Conclusions: Although the collection of hematopoietic progenitors and pretransplant evaluation are less expensive in autologous bone marrow transplantation, the early morbidity is higher than that of peripheral blood stem cell transplantation or mixed autotrasplanted of bone marrow and circulating progenitors thus resulting in higher costs.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been widely used after autologous peripheral blood stem cell transplant (APBSCT) in an attempt to reduce the duration of neutropenia, but whether this treatment has any influence on long-term engraftment remains unknown. We have retrospectively analyzed data from breast cancer patients to compare post-APBSCT rhG-CSF administration in terms of the short-term benefit and myeloid marrow regeneration after 1 year. Group A included 10 patients not treated with post-APBSCT rhG-CSF, while groups B and C comprised 15 and 13 patients treated with this drug from days +1 and +6, respectively. No differences among the three groups were found in age, diagnosis, previous chemo-radiotherapy, CD34+/CD71- cell concentration in pre-transplant bone marrow (BM), mobilization schedule, CD34+ cell yield, conditioning regimen and post-transplant radiotherapy. Post-APBSCT rhG-CSF was shown to accelerate neutrophil recovery, but there were no significant differences in platelet recovery, transfusion requirements, days of fever, antibiotic administration or inhospital stay. With regard to BM hematopoietic precursors 1 year after APBSCT, significantly lower concentrations of total CD34+cells, committed CD34+/CD33+ subsets, and more immature CD34+/CD71- cells were found in both groups B and C compared with patients not having received the cytokine (group A). Thus, post-APBSCT rhG-CSF administration does not appear to beneficially affect procedure outcome, and might even impair long-term marrow hematopoiesis. Bone Marrow Transplantation (2001) 27, 1287–1292. [ABSTRACT FROM AUTHOR]