Cutaneous involvement of disseminated adenovirus infection in an allogeneic stem cell transplant recipient.

Infection by human adenoviruses can lead to significant morbidity and mortality in immunocompromised hosts, such as allogeneic stem cell transplant (SCT) recipients, with limited effective treatment options. Specific cutaneous manifestations of disseminated adenovirus infection are not well described. We report a woman in her twenties who received an allogeneic T-cell-depleted peripheral blood SCT for the treatment of severe aplastic anaemia and, 5 months post-transplant, was hospitalized for severe systemic adenovirus infection with progressive involvement of the colon, liver and lungs. Despite therapy with intravenous cidofovir, oral brincidofovir and intravenous immunoglobulin, she had progression of adenoviraemia and dissemination of adenoviral disease. The patient developed a progressive rash characterized by keratotic papules that began on the palms and soles and spread to the entire body. Histopathological examination of skin biopsies of individual skin lesions from the palm and abdomen showed focal acantholytic dyskeratosis and keratinocytes with hyperchromatic nuclei. Several keratinocyte nuclei were immunoreactive for adenovirus. The patient was further treated with ribavirin and adenovirus-specific cytotoxic T lymphocytes but experienced multisystem progression of adenovirus infection culminating in death.

Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match.

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

Autoimmune hemolysis and immune thrombocytopenic purpura after cord blood transplantation may be life-threatening and warrants early therapy with rituximab.

Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10.4 months (range 5.8-24.5) post CBT for a 7% cumulative incidence 3 years after the day 100 landmark. Six patients presented with severe disease (hemoglobin ⩽6 g/dL and/or platelets <20 × 109/L). All AH patients were direct antiglobulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute GVHD. All 10 patients received rituximab 2-18 days after diagnosis, and corticosteroids combined with rituximab within <7 days was the most effective. No patient died of AH/ITP. AH/ITP occurs infrequently after CBT but may be life-threatening requiring emergency therapy. Rituximab combined with corticosteroids at diagnosis is warranted in patients with severe disease.

Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors.

Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes.

HIV-related thrombocytopenia.

Chronic thrombocytopenia is a common hematologic disorder in patients infected with the human immunodeficiency virus (HIV). Although often asymptomatic, the thrombocytopenia may be associated with a variety of bleeding abnormalities. The underlying pathophysiology includes accelerated peripheral platelet destruction and decreased ('ineffective') production of platelets from the infected megakaryocytes. HIV-related thrombocytopenia (HIV-TP) responds to antiretroviral therapy. Most studies have evaluated the use of AZT (zidovudine) and have shown increased platelet production. Combination therapy (HAART) also resulted in sustained platelet increases. When antiretroviral agents fail to improve the platelet count or cannot be used, other therapies, similar to those used in 'classic' immune thrombocytopenia (ITP), can be employed, including steroids, intravenous immunoglobulin (i.v.intravenous anti-D or splenectomy. Anti-D treatment offers advantages for HIV-TP because the duration of effect appears to be significantly longer than the response duration after i.v. therapy (initial results of our open-arm study were confirmed by our randomized trial). Of note, follow-up of heavily treated patients showed no acceleration of CD4 decline and no change in plasma viral load measurements. Splenectomy has been used to treat HIV-positive patients with refractory thrombocytopenia. Although it is effective therapy, there are concerns about infections and selection of appropriate candidates. Other treatment modalities, such as interferon, vincristine, danazol, low-dose splenic irradiation and staphylococcal protein A immunoadsorption have shown limited success in HIV-TP. Alternatively, thrombocytopenia in HIV-infected patients may be treated with pharmacological hyperstimulation of megakaryocytopoiesis (administration of PEG-rHuMGDF or TPO). Latest evidence indicates that the chemokine receptor CXCR4 (coreceptor for the cellular entry of lymphotropic HIV strains) is expressed on megakaryocytes; as a result, the development of chemokine receptor antagonists may modify the course of the disease.

Splenectomy-sparing, long-term maintenance with anti-D for chronic immune (idiopathic) thrombocytopenic purpura: the New York Hospital experience.

For nonsplenectomized children and adults with chronic or acute immune (idiopathic) thrombocytopenic purpura (ITP), anti-D has been shown to be a safe and effective treatment, providing hemostatic platelet increases in more than 70% of patients. Children had the best results, but all patient groups responded. In our recently published series, the effect of anti-D therapy lasted for more than 21 days in 50% of the responders and for more than 1 month in 37%. The use of anti-D as maintenance therapy was evaluated in a subset of patients. Of those who responded to the initial anti-D infusion, 79 patients (44 children, 35 adults) received 3 consecutive treatments. There were no significant differences in the responses after each infusion. Fifty-eight patients responded to all 3 treatments; of those, 20 (9 children, 11 adults) continued anti-D therapy, receiving an average of 18 infusions each (range, 10 to 36). The overall response rate was 86%. The ease of administration, duration of effect, and infrequent development of tachyphylaxis make anti-D an attractive alternative for maintenance therapy, particularly for children with ITP who have a high rate of spontaneous remissions. Use of anti-D as a means of spearing the spleen or, at least, postponing splenectomy should now be considered as a clinical option in the management of adult patients with chronic ITP.

Clinical experience with anti-D in the treatment of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease of children and adults, is characterized by low platelet counts and bleeding through mucous membranes. While not uncommon among otherwise healthy adults and children, ITP is a frequent complication of human immunodeficiency virus (HIV) infection. Anti-D is a gamma globulin (IgG) fraction containing a high proportion of antibodies to the Rh0 (D) antigen of the red blood cells. Clinical studies over the past 10 years have shown intravenous anti-D to be a safe and effective treatment for Rh-positive, nonsplenectomized patients with ITP (classic or HIV-related). While it is unlikely that anti-D is a curative treatment for ITP, repeated infusions can be used to maintain the platelet count at a level sufficient to provide adequate hemostasis (>30,000/microL) and may enable patients to postpone or even avoid splenectomy.

Donor-recipient allele-level HLA matching of unrelated cord blood units reveals high degrees of mismatch and alters graft selection.

The feasibility of selecting cord blood (CB) units at high-resolution HLA match has not been investigated. We analyzed the high-resolution donor-recipient HLA match of 100 double-unit 4-6/6 HLA-A,-B antigen, -DRB1 allele-matched CB grafts (units 1a and 1b) and their back-up units (n=377 units in total). The median cryopreserved graft dose was 2.9 × 10(7)/kg/unit, and at high resolution these units had a median donor-recipient HLA-allele match of 5/8 (range 2-8/8) and 6/10 (range 2-9/10), respectively. We then evaluated how often use of high-resolution HLA-match criteria would change the original graft selection to substitute one or both of the back-up units for units 1a and/or 1b. On using a model in which both a higher eight-allele HLA match and a cell dose ⩾ 2.0 × 10(7)/kg/unit were required, graft selection changed in 33% of transplants with minimal effect on cell dose (8.3% reduction). In summary, while units chosen based on HLA-A,-B antigen and -DRB1 allele match have substantial mismatch at higher resolution, CB selection based on high-resolution HLA match is possible in a significant proportion of patients without compromise in cell dose.

Importance of day 21 BM chimerism in sustained neutrophil engraftment following double-unit cord blood transplantation.

Delayed or failed engraftment remains a concern after cord blood transplantation (CBT) even when using double-unit grafts. Therefore, we analyzed the association between BM assessment performed approximately 21 days after transplantation, and the speed and success of sustained donor-derived neutrophil engraftment in 56 myeloablative double-unit CBT (DCBT) recipients. Overall, the cumulative incidence of sustained neutrophil engraftment was 95% (95% confidence intervals (CI): 89-100). Of the percentage of myeloid precursors, the BM cellularity and the total donor chimerism the total donor chimerism percentage had the most critical association with the speed and success of engraftment. DCBT recipients who were 100% donor achieved a 98% engraftment rate at a median of 22 days. This compared with 100% engraftment in patients who were 90-99% donor, but at a delayed median of 29 days and only 68% engraftment in patients <90% donor at a median of 37 days (P=0.001). Multivariate analysis was performed in the subgroup of patients who had not engrafted at the time the BM analysis was performed, the subgroup of most clinical concern. This confirmed donor chimerism was predictive of subsequent neutrophil recovery (P=0.004). These findings demonstrate the importance of the day 21 BM chimerism determinations after DCBT.

Factors affecting mortality following myeloablative cord blood transplantation in adults: a pooled analysis of three international registries.

A retrospective analysis was conducted to examine factors affecting early mortality after myeloablative, single-unit cord blood transplantation (CBT) for hematological malignancies in adolescents and adults. Data were collected from the three main CBT registries pooling 514 records of unrelated, single, unmanipulated, first myeloablative allogeneic CBTs conducted in North America or Europe from 1995 to 2005, with an HLA match ≥ 4/6 loci, in patients aged 12-55. Overall 100-day, 180-day and 1-year survival (Kaplan-Meier method) were 56, 46 and 37%, respectively, with no significant heterogeneity across registries. Multivariate analysis showed cell dose < 2.5 × 107/kg (odds ratio (OR) 2.76, P < 0.0001), older age (P = 0.002), advanced disease (P = 0.02), positive CMV sero-status (OR 1.37 P = 0.11), female gender (OR 1.43, P = 0.07) and limited CBT center experience (< 10 records contributed, OR 2.08, P = 0.0003) to be associated with higher 100-day mortality. A multivariate model predictive of 1-year mortality included similar prognostic factors except female gender. Transplant year did not appear as a significant independent predictor. This is the first analysis to pool records from three major CBT registries in the United States and Europe. In spite of some differences in practice patterns, survival was remarkably homogeneous. The resulting model may contribute to better understanding factors affecting CBT outcomes.

Evans syndrome. Results of a pilot study utilizing a multiagent treatment protocol.

PURPOSE: We evaluate the efficacy of combination medical therapy in the treatment of ITP and AIHA episodes for patients with Evans syndrome. PATIENTS AND METHODS: Five patients with Evans syndrome were followed for a median of 3.8 years and were treated according to our multiagent (IVIG, steroids, vinca alkaloids, androgens, and cyclosporin) protocol. RESULTS: All patients initially received IVIG and IV steroids for either acute hemolysis or thrombocytopenia. IV vinca alkaloids and oral Danazol were added in three patients for ITP. All responded, but two required frequently repeated vinca alkaloid treatments. Both patients treated with vinca alkaloids for severe hemolysis responded. Two patients received oral cyclosporin for refractory ITP; one had a transient response. Splenectomy was not included in our regimen. Two patients underwent splenectomy prior to their referral; both required further therapy. In addition, review of the clinical courses of our patients indicate that the DAT may be a prognostic factor for the chronicity of ITP. CONCLUSION: In view of the high relapse rates after splenectomy and the encouraging results of our pilot study, we suggest that medical treatment with combination agents (IVIG, steroids, vinca alkaloids, androgens and possibly cyclosporin) may provide a useful therapeutic approach to patients with Evans syndrome.

Suppression of erythropoiesis by intrauterine transfusions in hemolytic disease of the newborn: use of erythropoietin to treat the late anemia.

Hemolytic disease of the fetus and newborn has three phases of anemia: in utero, in the first week of life, and in the weeks and months after birth. Intrauterine transfusions can ameliorate the severity of both fetal and early anemia, but late anemia and the need for transfusion remain significant problems. Bone marrow hypoplasia--probably a result of suppression of erythropoiesis from the intrauterine transfusions--was documented in the three patients tested in our study. Because erythropoietin (EPO) levels have been found to be low (i.e., normal) in these previously transfused patients despite the degree of anemia, we treated four affected infants with EPO, 200 microliters/kg subcutaneously three times a week, and noted reticulocytosis and increased hemoglobin values 2 to 4 weeks later. One patient again had reticulocytopenic anemia when the EPO therapy was stopped but responded to retreatment. Our study indicates that EPO treatment may be effective in the management of late anemia and could help to decrease the need for postnatal transfusions.

Second malignant neoplasms in long-term survivors of childhood rhabdomyosarcoma.

BACKGROUND: The occurrence of second malignant neoplasms (SMNs) in successfully treated pediatric patients with cancer has been an area of increasing concern because survival of these patients has improved with intensification of therapy. Therefore, the incidence of SMNs in long term survivors of childhood rhabdomyosarcoma (RMS) was studied. METHODS: From 1970 to 1989, 210 newly diagnosed patients (median age, 9.7 years; range, 1 month to 27 years) with RMS were treated at Memorial Sloan-Kettering Cancer Center (New York, NY). Multimodality treatment included chemotherapy, surgery, and radiotherapy, when indicated. There were 130 long term survivors (> 2 years off therapy) with a median follow-up of 9 years (range, 2-20 years). The cumulative dose of each chemotherapeutic agent and the radiation doses each patient received were reviewed. Statistical analysis was performed by comparison with the Connecticut Tumor Registry data. RESULTS: Seven patients developed a SMN, including three with acute nonlymphoblastic leukemia (ANLL) and four with solid tumors. Acute nonlymphoblastic leukemia developed a median of 4.5 years after diagnosis. Of the solid tumors, 3 developed within the radiation field at a median of 10 years after diagnosis, whereas the fourth occurred 9.3 years after initial diagnosis in a patient who did not receive radiotherapy. All seven patients with SMNs received total dactinomycin doses higher than the median (9.6 mg/M2) for the group. All three patients with ANLL received total cyclophosphamide doses higher than the median (16.8 g/M2). Moreover, six of the seven patients received a dose of radiotherapy greater than 4000 cGy. The standardized incidence ratio was: 17.07 (95% confidence interval, 6.68-35.18; P < 0.0001). CONCLUSIONS: Multimodality therapy has improved long term survival for patients with childhood RMS. The combination of high dose radiotherapy and chemotherapy appears to increase the risk for developing a second malignancy.

Detection of maternal DNA in placental/umbilical cord blood by locus-specific amplification of the noninherited maternal HLA gene.

A critical issue regarding the broader utilization of placental/ umbilical cord blood (PCB) in unrelated bone marrow restoration is the possibility of contamination with maternal lymphocytes capable of immunological reactivity against the eventual recipient. On transplantation, such maternal cells might lead to graft-versus-host disease (GVHD) even if the intended donor's neonatal lymphocytes were unresponsive. We measured the proportion of PCB samples that were contaminated with maternal cells. Placental-maternal sample pairs were selected so that the mother was heterozygous for the DR53 haplotype, whereas the placental sample was DR53-negative. The PCB samples were investigated for the presence of the noninherited maternal gene DRB4, exclusive to the DR53 haplotypes. Locus-specific polymerase chain reaction amplification with DRB4 sequence-specific primers was followed by either gel electrophoresis or blotting and hybridization to an internal sequence DRB4 probe. Polymerase chain reaction products from DNA mixtures containing as low as 0.5 ng of a DRB4-positive DNA control in 1.0 microgram of a DRB4-negative DNA sample (1:2 x 10(3) dilution) showed a visible DRB4 band in agarose gels stained with ethidium bromide. Locus-specific hybridization increased the detection sensitivity to 1:10(5) (0.01 ng of the DRB4-positive DNA control). Control mixtures of known amounts of DRB4-positive and -negative DNA were included in all experiments. Comparison of the thickness of DRB4 bands after electrophoresis and the intensity of the DRB4-specific hybridization signals to the concentration controls allowed a rough estimation of the amount of maternal DNA in the placental blood specimens. A total of 213 PCB samples were tested. By gel electrophoresis, DRB4-specific bands were observed to be as strong or stronger in 23 (10.8%) samples as those in the 1:2 x 10(3) control, and 153 (17.8%) samples were negative in this test. The remaining 37 (17.3%) samples disclosed weaker DRB4 bands, suggesting the presence of maternal genetic material. By hybridization, 81 (38%) samples were positive and 132 were negative for the noninherited maternal gene. Review of the clinical characteristics of the mothers (demographics and labor and delivery information), the newborns (birth weight, sex, and gestational age), and PCB collections (placental weight, white blood cell count, and collected volume) failed to show any significant differences between the units testing positive or negative for the noninherited maternal gene. Thus, transplantable PCB units carry a high probability of having maternal DNA in detectable amounts. Whether this DNA comes from potentially graft-versus-host disease-inducing maternal lymphocytes or whether the putatively transplacentally-acquired maternal cells are immunologically dysfunctional, as in most infants with severe combined immunodeficiency disease, remains to be shown.

A murine model for human cord blood transplantation: near-term fetal and neonatal peripheral blood cells can achieve long-term bone marrow engraftment in sublethally irradiated adult recipients.

The purposes of the research reported here were first to explore a murine model for human placental and umbilical cord blood transplantation and second to evaluate the engraftment ability of ex vivo cultured hematopoietic cells. Murine near-term fetal and neonatal peripheral blood (FNPB) cells, genetically marked with the human multiple drug resistance transgene (MDR1) were used for syngeneic transplants into sublethally irradiated adult mice. Donor cells were transplanted either fresh and untreated, or after ex vivo culture in the presence of the hematopoietic growth factors recombinant murine stem cell factor, recombinant human interleukin-3 (rHu IL-3), and rHu IL-6, in a liquid culture system. To evaluate, count, and characterize FNPB progenitor cell-derived colonies, neonatal mouse mononuclear cells were cultured directly in methylcellulose with growth factors. To assess their ex vivo expansion ability, FNPB mononuclear cells were first cultured in liquid medium for 3 to 8 days and then transferred to semisolid assay plates. Evaluation of the cell counts after liquid culture showed a 1.4- to 11.6-fold increase, and the numbers of colonies observed in methylcellulose were similar to those produced by fresh FNPB cells. Donor-type engraftment was demonstrated by polymerase chain reaction (PCR) amplification of the human MDR1 transgene in the peripheral blood of all surviving animals (5 of 7 recipients of the fresh, and 3 of 8 recipients of the ex vivo-cultured cells) 2 to 4 months after transplantation. The proportion of donor leukocytes in the peripheral blood of the recipients (chimerism) was evaluated using fluorescence in situ hybridization (FISH) analysis 4 to 6 months after transplantation and ranged from 2% to 26%. In addition, bone marrow cultures were obtained from two recipient animals: one had received fresh-untreated cells and was evaluated 8 months after transplant, the other had received ex vivo cultured cells and was tested 14 months after grafting. The derived hematopoietic colonies were tested by PCR and the transgene was detected, conclusively proving long-term engraftment of donor cells. These results indicate that FNPB transplants can be successfully performed in sublethally irradiated mice with and without ex vivo culture. Long-term donor-type engraftment with sustained chimerism has been demonstrated. Thus, murine neonatal blood grafts can be used as an animal model for cord blood transplantation for gene therapy studies where complete myeloablation is not desirable and partial replacement of defective marrow may be sufficient. Furthermore, the possibility of numerically expanding hematopoietic progenitor cells contained in neonatal blood without affecting their engraftment ability could facilitate use of cord blood grafts in adult recipients.

Unrelated placental blood for bone marrow reconstitution: organization of the placental blood program.

The usefulness of placental/umbilical cord blood as a source of stem cells for marrow reconstitution of HLA-matched siblings has now been extended to the unrelated-donor setting. The need for HLA-matched donor tissue makes it essential to have available a frozen inventory of ready-to-use placental blood units. The New York Blood Center's Placental Blood Project, designed to evaluate the practical feasibility of unrelated placental blood transplantation, consists of four basic modules: collection of placental blood, maternal samples and donor data, accession and testing for genetic and infectious disease markers, freezing placental blood units, and data organization and retrieval. Additional modules include a computerized HLA matching algorithm and organization of data about patients requiring transplantation, which may be best taken up by organ-sharing organizations in the future. In this report, we describe the organization and discuss the methods and overall experience after collecting the first 1,000 units and supplying the tissue for the first two unrelated-donor placental blood transplants.

Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.

We report the results of intravenous anti-D (WinRho, WinRho SD) therapy in 261 non-splenectomized patients treated at the New York Hospital-Cornell Medical Center over the period from 1987 to 1994. Children (n = 124) and adult patients (n = 137) with classic immune thrombocytopenic purpura (ITP; n = 156) or human immunodeficiency virus (HIV) related thrombocytopenia (n = 105) and acute (n = 75) or chronic (n = 186) disease at the time of the initial anti-D treatment were studied. In addition, 11 previously splenectomized patients were treated as a separate group. Our objectives were to evaluate the following. (1) Efficacy of anti-D: The response after the initial infusion was analyzed according to clinical parameters, such as patient's age, HIV status, gender, disease duration, pretreatment platelet count, and hemoglobin value, as well as treatment-related factors, including the dose of anti-D, the solvent detergent treatment of the preparation, and the type of administration. (2) Use of anti-D as maintenance therapy: The duration of response after the initial infusion and the results of subsequent treatments were evaluated. (3) Safety/toxicity of anti-D: Postinfusion reactions and hemoglobin decrease after treatment were studied. Anti-D is a safe treatment providing a hemostatic platelet increase in greater than 70% of the Rh+ non-splenectomized patients. The group with the best results is HIV- children, but all patient groups respond and the effect lasts more than 21 days in 50% of the responders. Duration of response is not influenced by HIV status; furthermore, HIV+ patients show no adverse effects on hemoglobin decrease or HIV disease progression. Patients with chronic ITP after splenectomy have minimal or no response to intravenous anti-D.

Outcomes among 562 recipients of placental-blood transplants from unrelated donors.

BACKGROUND: A program for banking, characterizing, and distributing placental blood, also called umbilical-cord blood, for transplantation provided grafts for 562 patients between August 24, 1992, and January 30, 1998. We evaluated this experience. METHODS: Placental blood was stored under liquid nitrogen and selected for specific patients on the basis of HLA type and leukocyte content. Patients were prepared for the transplantation of allogeneic hematopoietic cells in the placental blood and received prophylaxis against graft-versus-host disease (GVHD) according to routine procedures at each center. RESULTS: Outcomes at 100 days after transplantation were known for all 562 patients, and outcomes at 1 year for 94 percent of eligible recipients. The cumulative rates of engraftment among the recipients, according to actuarial analysis, were 81 percent by day 42 for neutrophils (median time to engraftment, 28 days) and 85 percent by day 180 for platelets (median, day 90). The speed of myeloid engraftment was associated primarily with the leukocyte content of the graft, whereas transplantation-related events were associated with the patient's underlying disease and age, the number of leukocytes in the graft, the degree of HLA disparity, and the transplantation center. After engraftment, age, HLA disparity, and center were the primary predictors of outcome. Severe acute GVHD (grade III or IV) occurred in 23 percent of patients, and chronic GVHD occurred in 25 percent. The rate of relapse among recipients with leukemia was 9 percent within the first 100 days, 17 percent within 6 months, and 26 percent by 1 year. These rates were associated with the severity of GVHD, type of leukemia, and stage of the disease. CONCLUSIONS: Placental blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution.