Assessing the potential role of photopheresis in hematopoietic stem cell transplant.

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT).

More than 40,000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers and many community health-care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Blood and Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors.

The use of laparoscopic liver biopsies in pediatric patients with hepatic dysfunction following allogeneic hematopoietic stem cell transplantation.

Hepatic dysfunction following hematopoietic stem cell transplantation (HSCT) is common, but making the correct diagnosis can be challenging. Liver biopsies can serve as an important diagnostic tool when the etiology cannot be clearly determined by laboratory data, physical examination, and imaging studies. We reviewed 12 consecutive pediatric patients (seven males, five females, age 9-23 years) who received allogeneic HSCT and underwent a laparoscopic-guided liver biopsy for hepatic dysfunction of unknown etiology from 1998 to 2005. Biopsies were performed using a single-port technique with a 16 or 18 gauge, spring-loaded biopsy gun. The time from HSCT to biopsy ranged from 31 days to 821 days (median 92 days). No intra- or postoperative complications were observed. The initial clinical diagnosis was confirmed in seven patients, whereas the initial working diagnosis was inaccurate in the remaining five patients. Our results suggest that laparoscopic-guided liver biopsy is an informative and safe procedure in pediatric HSCT recipients; this approach helped delineate the true cause of hepatic dysfunction and changed our therapeutic approach in approximately 40% of the patients reviewed. While the safety record at our institution appears promising, a larger multi-institutional study would be necessary to more accurately describe the overall efficacy of this procedure in pediatric HSCT patients.

Reduced-intensity allogeneic hematopoietic stem cell transplantation for acute leukemias: 'what is the best recipe?'.

Reduced-intensity stem cell transplantation (RIST) has been shown to be a safe and useful alternative transplant method for patients including elderly and medically unfit patients. RIST conditioning regimens vary widely in the intensity of myeloablation, immunoablation, and antileukemia effects, and thus optimal regimen for each disease entity is yet to be determined. Most reports on RIST to date are small, single-institution experiences or retrospective studies with heterogeneous patient populations and primary diseases, complicating any direct comparison between studies. In acute myeloid leukemia (AML), moderate-intensity regimens may be effective, achieving 30-70% 1-year disease-free survival in various series, but minimal-intensity regimens are associated with high relapse rates. In acute lymphoblastic leukemia (ALL), not even moderate-intensity regimens are effective and most patients with advanced ALL relapse post transplant. Thus, the risk/benefit ratios of graft-versus-host disease/graft-versus-leukemia effect differ among diseases. Larger, prospective, multi-center clinical trials are needed to determine the best use of RIST in hematologic malignancies.

Stem cell transplantation in patients with severe congenital neutropenia with evidence of leukemic transformation.

Severe congenital neutropenia (SCN) is a hematologic condition characterized by arrested maturation of myelopoiesis at the promyelocyte stage of development. With appropriate treatment using recombinant human granulocyte-colony-stimulating factor (r-HuG-CSF), SCN patients are now surviving longer, but are at increased risk of developing myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but transplantation outcomes after malignant transformation are not well established. We report results for six patients with SCN who underwent HSCT for MDS or AML between 1997 and 2001 at two transplant centers. Two patients transplanted for MDS survived. Both of these patients were transplanted without being given induction chemotherapy. Four patients, who all received induction chemotherapy for AML prior to HSCT, died. Administering induction chemotherapy prior to HSCT resulted in significant morbidity. Rapid transplantation should be the goal for the SCN patient once the diagnosis of MDS/AML is established. SCN patients should be monitored carefully for progression to MDS in order to be treated with HSCT as soon as they have progressed and before developing AML. For SCN patients who progress to AML, HSCT should still be considered, even though the risks appear to be greater.

West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation.

We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.

A phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation.

Interleukin-11 (IL-11) decreases cytokine release and increases survival in murine BMT models. In these systems, it reduces gut permeability, partially polarizes T cells to a Th2 phenotype, down-regulates IL-12, prevents mucositis, and accelerates recovery of oral and bowel mucosa. We conducted a randomized double-blind pilot study of rhIL-11 administered with cyclosporine/MTX prophylaxis after cytoxan/TBI conditioning and allogeneic stem cell transplantation for hematologic malignancies. Patients received rhIL-11, 50 microg/kg subcutaneously daily or placebo in a 3:1 ratio. Treatment was administered prior to the start of conditioning and continued up to 21 days. The study was designed to assess safety with stopping rules for cardiac arrhythmias and mortality. Although projected to accrue 20 patients, only 13 patients (10 IL-11, three placebo) were enrolled because the early stopping rule for mortality was triggered. Of 10 evaluable patients who received IL-11, four died by day 40 and one died on day 85. Deaths were attributable to transplant-related toxicity. One of three placebo recipients died of suicide, the other two are alive. Patients receiving IL-11 had severe fluid retention and early mortality, making it impossible to determine whether IL-11 given in this schedule can reduce the rate of GVHD. Grade B-D acute GVHD occurred in two of eight evaluable patients on IL-11 and one of three patients on placebo. The primary adverse events of the study were severe fluid retention resistant to diuresis (average weight gain 9 +/- 4%) and multiorgan failure in five of 10 evaluable patients. The use of IL-11 as GVHD prophylaxis in allogeneic transplantation cannot be recommended as administered in this trial.