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Biomedical subjects

Robert Iannone

Publications and source records attributed to Robert Iannone.

8 recordsLinked to original sources
PubMed2006

Weighing the risks of G-CSF administration, leukopheresis, and standard marrow harvest: ethical and safety considerations for normal pediatric hematopoietic cell donors.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is used for collection of hematopoietic cells in most adult and a smaller but significant percentage of pediatric normal donor harvests. Short and long-term risks of G-CSF administration and leukopheresis are not well understood in the pediatric population. PROCEDURE: Literature review including observations from the IBMTR, NMDP, EBMT, German Donor Registry, and the authors' work. RESULTS: G-CSF causes temporary discomfort in a minority of younger donors. Rare serious side effects of G-CSF have yet to be reported in children. To date, an increase in hematological malignancies after short-term G-CSF use has not been detected in adult donors and no cases have been reported in children. Reported complications of leukopheresis in children are rare and minor, but donors <20 kg may be exposed to allogeneic blood products. Pediatric aged donors vary widely in their ability to assent or consent to the risks of a donation procedure. There are key regulations and ethical imperitives, which must be addressed in deciding which donation procedures are appropriate for minors. CONCLUSIONS: While short term administration of G-CSF and leukopheresis appear to be safe and effective procedures when used to assist in collection of a hematopoietic cell graft from a normal pediatric donor, institutions adding or substituting one or both of these procedures for standard marrow donation must decide whether the donor should be considered a research subject, and if so, whether the new procedures are a minor increase over minimal risk. Because these procedures are being performed on and off study at many pediatric centers, a comprehensive study addressing donor safety could help clarify risks of rare adverse events.

Bone Marrow Transplantation↗
PubMed2005

Tissue typing for hematopoietic cell transplantation: newer techniques and newer antigens for which cross-matching is helpful.

Refinements in human leukocyte antigen (HLA) typing techniques for hematopoietic cell transplantation (HCT) have permitted a more precise assessment of donor-recipient histocompatibility, which has impacted transplantation outcomes. More recently, differences in transplant outcomes associated with killer immunoglobulin-like receptor compatibility have emphasized the potential importance of natural killer (NK) cell typing in HCT. This article reviews the current state of the art for HCT donor selection based on both HLA and NK cell typing.

Blood Grouping and Crossmatching↗
PubMed2004

Pulmonary hypertension complicating bone marrow transplantation for idiopathic myelofibrosis.

Idiopathic myelofibrosis is a rare hematologic disorder that is occasionally associated with pulmonary hypertension and has been cured with bone marrow transplantation (BMT). Most cases occur in older adults, but children with similar clinical and pathologic findings have been described. The authors describe a critically ill male infant with idiopathic myelofibrosis and subtle findings suggestive of pulmonary hypertension who was treated with BMT after failing to respond to chemotherapy. After BMT, the patient's clinical course improved in all respects, but he ultimately died of progressive pulmonary hypertension.

Bone Marrow Transplantation↗
PubMed2003

Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia.

We describe previously transfused patients with sickle cell disease (n = 6) and thalassemia (n = 1) who received nonmyeloablative hematopoietic stem cell transplantation (HCT) to induce stable (full or partial) donor engraftment. Patients were 3 to 20 years (median, 9 years) old. All 7 received pretransplantation fludarabine and 200 cGy of total body irradiation; 2 patients also received horse antithymocyte globulin. Patients received bone marrow (n = 6) or peripheral blood stem cells (n = 1) from HLA-identical siblings, followed by a combination of mycophenolate mofetil and cyclosporine or tacrolimus for postgrafting immunosuppression. After nonmyeloablative HCT, absolute neutrophil counts were <0.5 x 10(9)/L and <0.2 x 10(9)/L for a median of 5 days (range, 0-13 days) and 0 days (range 0-13 days), respectively. A median of 0 (range, 0-9) platelet transfusions were administered. No grade IV nonhematologic toxicities were observed. One patient experienced grade II acute graft-versus-host disease. Two months after transplantation, 6 of 7 patients had evidence of donor chimerism (range, 25%-85%). Independent of red blood cell transfusions, these 6 patients initially had increased total hemoglobin and hemoglobin A concentrations and a reduction of reticulocytosis and transfusion requirements. There were no complications attributable to sickle cell disease during the interval of transient mixed chimerism. However, after posttransplantation immunosuppression was tapered, there was loss of the donor graft, and all patients experienced autologous hematopoietic recovery and disease recurrence. One patient did not engraft. The duration of transient mixed chimerism ranged from 97 to 441 days after transplantation in patients 4 and 6, respectively, and persisted until immunosuppressive drugs were discontinued after transplantation. In summary, the nonmyeloablative HCT regimens described here produced minimal toxicity and resulted in transient donor engraftment in 6 of 7 patients with hemoglobinopathies. Although complications from the underlying hemoglobinopathies did not occur during the period of mixed chimerism, these results suggest that stable (full or partial) donor engraftment after nonmyeloablative HCT is more difficult to achieve among immunocompetent pediatric patients with hemoglobinopathies than among adults with hematologic malignancies, perhaps in part because recipients may have been sensitized to minor histocompatibility antigens of their donor by preceding blood transfusions.

Adult↗
PubMed2003

Hematology grants workshop.

Uppermost among the many concerns of young researchers is acquiring funding for beginning a career as a clinician-scientist. This chapter is targeted specifically at those individuals considering an academic physician-scientist career and those on the verge of becoming independent researchers. In Section I, Drs. Poncz and Iannone discuss the Mentored Career Development Award (K08). They summarize the application process, highlighting the critical components of a successful application and what the review process entails. In Section II, Dr. Werner discusses what applicants need to know about the NIH Institutes' program, review, and grants management function; the different NIH staff whom applicants should contact during the various stages of the grants process; and the important sections and key phrases in NIH Program Announcements for career development awards.

Consensus Statements as Topic↗
PubMed2002

Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation.

Cyclophosphamide (Cy) has been studied extensively for its immunosuppressive properties and is frequently combined with total body irradiation (TBI) as conditioning prior to HLA-identical allogeneic blood or marrow transplantation (alloBMT) in humans. Because Cy is most effective at suppressing host-versus-graft reactions when the drug is given after the transplantation (Mayumi H et al. Transplant Proc. 1986;18:363-369), we investigated whether posttransplantation Cy could prevent rejection of allogeneic marrow in mice conditioned with low-dose TBI. In a mouse model, posttransplantation Cy reduced the dose of TBI required from 500 cGy to < or = 200 cGy for the engraftment of 10 million major histocompatibility complex (MHC)-identical marrow cells in 100% of recipients. In animals conditioned with low-dose TBI and posttransplantation Cy, donor chimerism was proportional to the dose of TBI, was present in multiple hematopoietic lineages, and was associated with the indefinite survival of donor-strain skin grafts. In contrast, animals conditioned with either TBI alone or posttransplantation Cy alone failed to achieve engraftment after alloBMT and contained antidonor cytotoxic T-cells. Although <5% donor chimerism could be induced without TBI by transplanting > or = 50 million MHC-identical cells and administering posttransplantation Cy, the addition of low-dose TBI reduced the dose of donor cells required for alloengraftment and increased long-term donor chimerism to >50%. These data demonstrate that low-dose TBI and posttransplantation Cy cooperate to prevent graft rejection following the transplantation of standard doses of MHC-identical marrow cells.

Animals↗