Central nervous system (CNS) tuberculosis following allogeneic stem cell transplantation.

Tuberculosis is an uncommon infectious complication after stem cell transplantation. We report a patient who presented with a brain mass, 3 months after pulmonary tuberculosis had been diagnosed and while he was receiving triple antituberculous therapy. He had extensive chronic GVHD. The diagnosis was made after biopsy of the lesion. The cerebral mass was excised, antituberculous treatment was maintained and the patient made a complete neurologic recovery. Six months later, he died of gram-negative septic shock. Mycobacterial infections should be considered in allograft recipients with chronic GVHD and solid lesions in the brain. Bone Marrow Transplantation (2000) 25, 567-569.

Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection.

Up to a third of autologous transplantation candidates fail to mobilize hematopoietic progenitors into the peripheral blood with chemotherapy and/or growth factor treatment, thus requiring innovative mobilization strategies. In total, 20 cancer patients unable to provide adequate PBPC products after a previous mobilization attempt were treated with ancestim (20 microg/kg/day s.c.) and filgrastim (10 microg/kg/day s.c.). In 16 patients, the pre-study mobilization was with filgrastim alone. Eight patients underwent single large volume leukapheresis (LVL) and 12 multiple standard volume leukaphereses (SVL) in both mobilizations. Pairwise comparison of peripheral blood CD34(+) cell concentrations on the day of first leukapheresis failed to document synergism - median CD34(+)/microl of 3.2 (<0.1 to 15.4) and 4.5 (1-28.56) for the pre-study and on-study mobilizations (P = 0.79, sign test), and 4.2 (<0.1-15.4) and 5 (1-28.56), respectively, for the 16 patients previously mobilized with filgrastim alone (P = 1, sign test). The number of CD34(+) cells/kg collected per unit of blood volume (BV) processed was similar in both mobilizations - median 0.1 x 10(6)/kg/BV and 0.09 x 10(6)/kg/BV, respectively (P = 1, sign test). In this phase II study, the combination of ancestim and filgrastim did not allow adequate PBPC mobilization and collection in patients with a previous suboptimal PBPC collection.

Autologous stem cell transplantation in a patient with severe systemic sclerosis.

UNLABELLED: Systemic Sclerosis (SSc) is a chronic disease of the connective tissue, whose pathogenesis involves abnormalities of the immunological system. It has a variable course and there is a subgroup of patients with rapidly progressive disease or unresponsive to conventional treatment. These patients can benefit from intensive immunosuppression and autologous hematopoietic stem cell transplant. CLINICAL CASE: 19-year-old (y.o.) woman diagnosed with SSc at the age of 13 y.o. with cutaneous, vascular and articular involvement with initial response to methotrexate. Three years later the disease progressed with severe digestive involvement (dysphagia, delayed gastric emptying and weight loss) needing gastrostomy for nutritional support. She was treated with cyclophosphamide without improvement In May 2012 she had an autologous transplant with myeloablative regimen (BEAM): carmustine 300 mg/m2x1 day; etoposido 120 mg/kgx4 days; cytarabine 120 mg/kg 12/12:hx4 days; melphalan 140 mg/m2x1 day. A year and a half after transplantation she is asymptomatic, without any signs or symptoms of the disease, feeds by mouth and the gastric emptying study is normal. Currently she is free of medication.

Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.

Predictive value of immature reticulocyte and platelet fractions in hematopoietic recovery of allograft patients.

Hematopoietic progenitor cell transplantation is the treatment of choice for patients with malignant hematologic diseases. Neutrophil (NEUT) and platelet (PLT) counts are used to evaluate hematologic engraftment of transplanted patients. Recent-generation hematology analyzers offer an alternative way to evaluate immature peripheral blood (PB) cell fractions, which may also give an indication of hematopoietic recovery. The immature reticulocyte fraction (IRF) and immature platelet fraction (IPF) in PB samples may provide early indicators of transplant success. We evaluated the predictive value of IRF and IPF for the hematologic recovery of 46 adult patients undergoing allogeneic PB progenitor cell transplantation. We observed that IRF recovery anticipated by 4 days compared with NEUT recovery (11 vs 15 d) and IPF by 2 days compared with PLT (10 vs 12 d). The recovery was different for patients undergoing a nonmyeloablative regimen (NMA); we observed an early IRF recovery by 5 days compared with NEUT (10 vs 15 d) and a IPF compared with PLT recovery by 2 days (9 vs 11 d). We also observed significant correlations between NEUT and PLT recovery with recoveries of the new parameters IRF and IPF. We concluded that IRF and IPF predicted hematopoietic recovery. For allografted patients after NMA regimens, prediction was even more clinically relevant. These immature fractions open new perspectives for monitoring patient transfusion support through the posttransplantation recovery.

Mobilization and collection of peripheral blood stem cells in multiple myeloma patients older than 65 years.

Over the past 10 years, the incidence of multiple myeloma (MM) has been greater among individuals >65 years old than in younger age groups. This retrospective study of peripheral blood stem cell mobilization and harvesting examined patients of various age groups who were afflicted with this pathology. One group of 17 patients ≥65 years of age with MM (group A) were mobilized between 2002 and 2009 and compared with 33 consecutive patients of younger ages with the same diagnosis treated in 2008 and 2009 (group B). The 2 populations had a similar gender distribution; their median ages were 66 and 52 years, respectively. A successful mobilization was defined as a collection of ≥2.5 × 10(6) CD34+/kg body weight. The mobilization used filgrastim (16 µg/kg/d) with the beginning of the harvest on the fifth day. The median number of outpatient apheresis procedures per patient was 2 in group A and 1 in group B. There were no incidents or serious adverse reactions. Patients in group A collected 4.68 × 10(6) CD34+ cells/kg and for group B 3.30 × 10(6)/kg. The group A patients required a greater number of apheresis procedures to collect the appropriate graft. In conclusion, mobilization with growth factors and PHSP harvest by apheresis was safe with reasonable costs for subjects including those aged ≥65 years, resulting in an option for autologous transplantation.

Bleeding events and mortality in SCT patients: a retrospective study of hematopoietic SCT patients with organ dysfunctions due to severe sepsis or GVHD.

In autologous and allogeneic hematopoietic SCT (HSCT) neutropenia may be associated with severe infection. Immunodeficiency associated with GVHD and its treatment in allogeneic HSCT is also a risk for severe infection. In both periods, patients may develop severe sepsis with organ failure. To gain insights into treatment possibilities, HISTORY, a multicenter retrospective study reviewed HSCT patient records on mortality, organ dysfunction, platelet count and bleeding events. All transplantation records from 16 European centers were reviewed for 1.5 years. Of 2092 patients screened, 160 were documented for HSCT with respiratory and/or cardiovascular organ dysfunction because of sepsis and/or GVHD. Mortality was 53.1% at 28 days and 65.6% at 100 days. HSCT patients with sepsis and organ dysfunction are at highest risk of death (49.5%). Death from refractory septic shock was 15.2%, and it was 20% from respiratory failure and 64.7% from sepsis. Fewer than 3% of HSCT patients died from bleeding complications; however, individuals at increased risk of bleeding were excluded. Despite low platelet counts, an increased risk of bleeding could be established only if thrombocytopenia dropped below 13 x 10(9)/l. Thus, there might be a therapeutic window for treatment strategies for severe sepsis in HSCT, such as drotrecogin alpha (activated).

The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings.

This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14. 9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34(+) and CD3(+) cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3(+) cells in the inoculum. Twenty-three of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 x 10(6)/kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 x 10(6)/kg (actuarial probability 18% vs 1%, respectively; P =.0001). The actuarial probability of graft failure progressively increased as the number of CD3(+) cells in the graft decreased, which was determined by grouping the number of CD3(+) cells in quartiles (log-rank P =.03; log-rank for trend P =.003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3(+) cells less than or equal to 0.2 x 10(6)/kg (risk ratio = 17; P <.0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P =.001). From these results it appears that the number of CD3(+) cells in the inoculum-with a threshold of 0.2 x 10(6)/kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34(+) from HLA-identical siblings. In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens.