Ralph Quinones

Clinical and In Vitro Evaluation of Cidofovir for Treatment of Adenovirus Infection in Pediatric Hematopoietic Stem Cell Transplant Recipients

Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had severe manifestations of infection. Cidofovir treatment led to clinical improvement in 8 of 10 patients with severe infection and to virologic clearance in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12 clinical adenovirus isolates. Cidofovir is a promising treatment option for this population.

Pulmonary veno-occlusive disease after autologous bone marrow transplant in a child with stage IV neuroblastoma: case report and literature review.

Pulmonary veno-occlusive disease (PVOD) is a rare, almost universally fatal complication of chemotherapy and bone marrow transplantation with few treatment options. A 19-month-old boy with stage 4 neuroblastoma with fatal PVOD following high-dose chemotherapy with autologous peripheral blood stem cell rescue is described here. A comprehensive literature review revealed 40 case reports of PVOD in oncology patients. Various therapeutic modalities were attempted, with four survivors. PVOD should be considered in patients with dyspnea and cardiomegaly. Less invasive diagnostic methods and more effective therapies are needed.

Hematopoietic engraftment and graft failure after bone marrow transplantation.

Purpose : This article reviews the complex process of establishing functional long-term hematopoiesis required for successful clinical bone marrow transplantation. The failure to establish sustained hematopoiesis, either primary or secondary graft failure, is defined and multiple etiologic factors involved are discussed. Design : Data from published studies of experimental and clinical BMT, as well as in vitro stem cell biology, were used to elucidate the elements required for establishing functional hematopoiesis. These include pleuripotential hematopoietic stem cells; homing of stem cell to the hematopoietic micro-environment; hematopoietic stroma and secreted cytokines acting synergistically to promote expansion and hematopoietic differentiation of the stem cells; and, in the setting of allogeneic transplantation, immunological tolerance between the host and the graft, without which graft rejection or graft-vs.-host disease may occur. Conclusions: The factors influencing the establishment of functional hematopoiesis and the risks for graft failure vary with the type of transplant performed. In an autologous transplant, damage to the stem cells or to the stroma microenvironment can contribute to prolonged time to engraftment or primary graft failure. In contrast, the hematopoietic stem cells are normal in both syngeneic and allogeneic transplantation. However, in the latter, because of immunological disparity between the host and recipient, there can be either primary or secondary graft failure due to a host-vs.-graft phenomenon, graft rejection. Classic graft rejection is an immunologic phenomenon mediated by residual host immunocompetent cells, either T cells or NK cells, depending on the allogeneic disparity between host and donor. T cell depletion and increased HLA disparity are risk factors for rejection. Numerous strategies have attempted to decrease the risk of rejection; most have focused primarily on increased immunosuppression of the host either with additional radiation, chemotherapy or in vivo anti-T cell serotherapy. Recent attempts have explored preventing rejection by manipulating donor cell composition of the infused graft.

Successful cord blood transplantation for sickle cell anemia from a sibling who is human leukocyte antigen-identical: implications for comprehensive care.

We report the successful transplantation of umbilical cord blood stem cells from a sibling who is human leukocyte antigen-matched to a child with sickle cell anemia. Conditioning was with busulfan, cyclophosphamide, and antithymocyte globulin. Time to neutrophil count >500/&mgr;L was 23 days and to platelet count >50,000/&mgr;L was 49 days. Full donor engraftment was achieved without graft-versus-host disease. This case demonstrates the potential usefulness of harvesting cord blood from full siblings of patients with sickle cell disease. Routine collection of umbilical cord blood from siblings should be considered for patients with sickle cell disease, and may increase acceptance and use of transplantation by families.

Abnormal Infant Pulmonary Function in Young Children With Neuroendocrine Cell Hyperplasia of Infancy

Lung function in children with neuroendocrine cell hyperplasia of infancy (NEHI) and correlations with future clinical outcomes are needed to guide clinical management.

Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT)

Summary:Pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with monosomy 7 is associated with poor disease-free survival when treated by conventional chemotherapy, immunosuppression or supportive measures. Hematopoietic stem cell transplant (HSCT) may improve outcomes; however, data to support this are limited. To better understand the curative potential of HSCT in these patients, all cases of AML and MDS with monosomy 7 treated by two transplant programs (1992 to present) were reviewed. A total of 16 patients were treated, all by allogeneic HSCT. Primary diagnoses were MDS (N=5), therapy-related MDS (N=3), AML (N=5) and therapy-related AML (N=3). In all, 11 patients (69%) survive event-free at 2 years with median follow-up of 986 days (range 330–2011 days). Toxicity caused deaths of the five nonsurviving patients, four of whom were transplanted with active leukemia. Allogeneic HSCT is effective therapy for childhood AML and MDS associated with monosomy 7, particularly for patients with AML in complete remission and MDS.

Cord blood transplant in childhood ALL

Optimal therapy for high risk and relapsed acute lymphoblastic leukemia (ALL) remains uncertain. Wider availability of cord blood from related and unrelated donors has prompted studies of its use for hematopoeitic stem cell transplant (HSCT).

GVHD after unrelated cord blood transplant in children: characteristics, severity, risk factors and influence on outcome

We reviewed our experience in 79 children who had unrelated cord blood transplant (UCBT) between 1996 and 2007 with a major focus on GVHD, comparing both traditional and National Institute of Health (NIH) criteria. The cumulative incidence (CI) of acute GVHD (aGVHD, by day +100) was 0.42 for grade II–IV and 0.22 for grade III–IV. The CI of all aGVHD (NIH, that is, no time limit) at 1 year was 0.45 for grade II–IV and 0.32 for grade III–IV. Infused CD34 cell dose (>1 × 105/kg), pretransplant bacterial infection and nonmalignant disorders were risk factors for grade II–IV aGVHD on univariate analysis. Infused CD34 cell dose remained significant on multivariate analysis. At 1 year, the CI of chronic GVHD (cGVHD) using the Seattle criteria was 0.27, whereas that for cGVHD (NIH) was 0.08. By NIH criteria, the classic form of cGVHD was uncommon (5%) after UCBT. Instead, the acute (71%) and overlap (24%) GVHD variants predominated. Grade II–IV aGVHD was a significant risk factor for cGVHD by both Seattle and NIH criteria. We conclude that GVHD after day +100 after UCBT typically carries features of aGVHD. Moreover, and in marked contrast to adult unrelated donor hematopoietic stem cell transplantation, the GVHD observed in this series did not adversely affect survival.

Dual ALK and MYC rearrangements leading to an aggressive variant of anaplastic large cell lymphoma.

Anaplastic lymphoma kinase (ALK) and MYC are oncogenes often dysregulated in pediatric lymphomas. NPM-ALK/t(2;5)(p23;q35) is a genetic hallmark of ALK+ anaplastic large cell lymphoma (ALCL). MYC gene translocations are frequently detected in high-grade B-cell lymphomas. ALK+ALCL cases with concurrent MYC translocation are exceedingly rare and are more aggressive and chemoresistent compared with other ALK+ALCL. We report a patient who presented with ALK+ALCL possessing coexistent MYC rearrangement, massive tumor dissemination, and early widespread relapse. This case underscores the importance of recognition of close correlation between dual ALK and MYC rearrangements and the characteristic clinical features in this unusual ALCL variant.

Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation

Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the no wash or dilution only techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.