Functional properties of flours and protein concentrates of 3 strains of the edible mushroom Pleurotus ostreatus.

Pleurotus ostreatus is an edible mushroom with significant nutritional properties and highly valuable protein concentrates can be obtained from its fruit bodies. Functional properties of flours and protein concentrates derived from 3 Pleurotus ostreatus strains (PCM, POS and hybrid PCM × POS) were evaluated in this investigation. Fruit bodies were produced on wheat straw substrate, flours were obtained from dried and grinded fruit bodies and protein concentrates were extracted from flours by alkaline solubilization. For all 3 strains, pale yellow flours were obtained and protein concentrates showed a grayish brown color. Flour bulk densities ranged from 0.52 to 0.64 g/mL, a higher value than those for protein concentrates, i.e. 0.30-0.35 g/mL. The highest water absorption capacities (WAC) were observed for flours (300-418.8%) while protein concentrates presented higher oil absorption capacity (OAC) (173.3-214.1%). Flours and protein concentrates presented a minimal gelation concentration of 2%. Protein concentrates showed a higher foam capacity formation (FC) at pH 8. Likewise, flours and protein concentrates presented higher foam stability (FS) at alkaline pH (8 and 10). Emulsion activity index (EAI) for flours ranged from 3.96 to 26.68 m2 g-1 whereas for protein concentrates ranged from 1.55 to 10.28 m2 g-1. These results indicate that flours and protein concentrates from P. ostreatus have remarkable functional properties, valuable in food industry where foaming and emulsifying properties are required.

Spasmolytic effect of Alternanthera repens on isolated rat ileum.

Abstract Context: Alternanthera repens (L.) Kuntze (Amaranthaceae) is widely used in Mexican traditional medicine for the treatment of gastrointestinal disorders that are mainly related to diarrhea. Objective: The aim of the present study was to investigate the spasmolytic effect of hexane (Hx), methanol (Me) and aqueous (Aq) extracts as well as chromatographic Me fractions (F1-F6) of A. repens in rat ileum. Materials and methods: Dried and powdered aerial parts were used to obtain the extracts. The rat ileum preparations were incubated in Tyrode's solution gassed (95% O2-5% CO2) at 37 °C. The effect on the contractile response of isolated ileum was evaluated by obtaining cumulative concentration-response curves to CaCl2, KCl, 5-HT and acetylcholine in the absence and presence of different doses of Aq (0.56-2.09 mg/mL), Me (0.24-0.91 mg/mL) and Hx (0.24-0.91 mg/mL) extracts, as well as six Me fractions of 0.66 mg/mL (F1 to F6). Results: The A. repens Me (0.24 mg/mL) caused an inhibitory response of the Ca2+-induced contractions, with IC50 values of 0.18 ± 0.061 and 0.67 ± 0.061 mM in the presence and absence of the Me, respectively. Me fractions F2 to F4 presented a significant inhibitory effect (F(3,8) = 60.17, p = 0.0001), causing a reduction in the CaCl2-induced contractions and shifting the Ca2+ (0.39 to 1.81 mM) concentration-response curves to the right. With respect to the effect on 5-HT-induced contractions, IC50 values Hx extract (0.24 mg/mL) were 5.44 ± 0.08 × 10-6 M and 3.38 ± 0.07 × 10-6 M in the presence and absence of the Hx, respectively. Discussion and conclusion: The spasmolytic effects induced by Me and Me fractions of A. repens may involve a serotonergic and Ca2+ influx blockade mechanisms, which may justify the use of A. repens extracts as an effective traditional treatment against diarrhea.

An unusual case of donor-derived myelodysplastic syndrome following double-unit umbilical cord blood transplantation in acute lymphoblastic leukemia.

Umbilical cord-blood transplantation is considered an effective treatment strategy for acute lymphoblastic leukemia (ALL) when a human leukocyte antigen (HLA)-matched donor is unavailable. The use of a second unit helps ensure engraftment in larger adults and those with comorbidities, even though only one unit engrafts in most patients. Herein, we present the clinical and laboratory characteristics of a patient who developed donor-derived myelodysplastic syndrome (ddMDS) after double umbilical cord-blood transplantation (dUCB HSCT). To our knowledge, no cases of ddMDS have been described in a patient with a history of ALL in molecular remission after receiving a dUCB HSCT. Current molecular techniques, including analysis of short tandem repeats (STR) and fluorescence in situ hybridization (FISH) allowed us to firmly establish donor origin.

Barriers to conceiving sibling donors for sickle cell disease: perspectives from patients and parents.

OBJECTIVES: The lack of matched sibling donors poses a significant barrier to utilizing hematopoietic cell transplantation (HCT), the only proven cure for children with sickle cell disease (SCD). Little is known about current patient and parent perspectives towards HCT for SCD. This study examines the perceived barriers of transplant, and the use of in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD), when there is no pre-existing sibling donor. DESIGN: Semi-structured interviews were conducted with adult patients with SCD and parents of children with SCD in an urban medical center in the US. Transcribed data was analyzed using qualitative methods. RESULTS: Of 23 participants, 17 reported having heard of HCT for SCD. Fewer knew of IVF or PGD as a means for conceiving an unaffected child (n =7) or to select a potential umbilical cord blood donor (n =1). The financial cost of IVF and PGD was perceived as a significant initial barrier to accessing these technologies, with the clinical risks of HCT and the ethical appropriateness of using PGD also identified as barriers. The value of informing families of these options was a recurring theme, even among respondents who personally disagreed with their application. CONCLUSION: The low utilization of curative strategies for SCD appears to be partly attributable to a lack of information about the technologies available to facilitate transplantation. Ethical reservations, while present, were not static and did not preclude patients' and parents' desire to be informed. We discuss the implications of these perceived barriers to the dissemination of advanced medical technologies for SCD.

A novel coconut-malt extract medium increases growth rate of morels in pure culture.

Morels are gourmet wild edible mushrooms that can grow on several substrates with significant growth rate variations. Such variations have hindered the development of a standardized culture media to promote morel's sustainable production. The aim of this study is developing a novel culture media that takes advantage of coconut water as a complementary component of culture media. Coconut water has been extensively used as a growth-promoting component for plant tissue cultures; however, its application as component of fungi cultivation medium has not been fully developed. This study confirms that coconut water can be efficiently used as culture media component for morels using a kinetic characterization. Morchella sp. kinetic growth is evaluated in different cultures: agar, malt extract agar (MEA), lactose, coconut water (15%) and combinations of them. Kinetic growth parameters (lag phase, λ and maximum specific growth rate, µmax) are estimated using primary modeling methods. Among the selected models, the best fit is achieved using Baranyi's model. A significant increase from 15.8% to 43.4% of the µmax values was observed when culture media (agar, lactose, MEA) is supplemented with coconut water. The largest values of µmax are obtained in MEA-coconut cultures (21.13 ± 0.43-22.57 ± 0.35). Micro-sclerotia and late sclerotia are observed in all cultures containing coconut water justifying the development of a feasible and cost-effective way of culturing morels. The results demonstrate that coconut water can be used for formulation of standard media for morel cultivation leading to a cheap alternative to produce dense mycelium and promote sclerotia formation.

Rhizomucor variabilis var. regularior and Hormographiella aspergillata infections in a leukemic bone marrow transplant recipient with refractory neutropenia.

Rhizomucor variabilis and Hormographiella aspergillata rarely cause human infections. This report details a fatal case of a 14-year-old female with leukemia posthematopoietic cell transplant and relapse with refractory pancytopenia. The patient first developed an R. variabilis var. regularior palate infection and later developed a cutaneous H. aspergillata infection while on posaconazole and caspofungin therapy.

Sequential administration of sargramostim and filgrastim in pediatric allogeneic stem cell transplantation recipients undergoing myeloablative conditioning.

G-CSF and GM-CSF both hasten myeloid engraftment post-MA-alloSCT; however, GM-CSF is earlier acting and less expensive. The objective was to evaluate efficacy/safety of sequential administration of GM-CSF followed by G-CSF in children post-MA-alloSCT. From January 2001 to June 2005, 31 children received 32 MA-alloSCT: mean age 6.65 yr; MRD BM or PBSC vs. related or unrelated UCB 11:21; malignant vs. non-malignant disorders 22:10. GM-CSF (250 microg/m(2) IV QD) began on day of stem cell infusion. GM-CSF was switched to G-CSF (10 microg/kg IV QD) when WBC >or= 300/mm(3) x 2 days. G-CSF continued until ANC >or= 2500/mm(3) x 2 days, then tapered to maintain ANC >or= 1000/mm(3). Median time to myeloid engraftment (ANC >or= 500/mm(3) x 3 days) was 17 days [13 days vs. 24 days, MRD BM/PBSC vs. UCB (p < 0.0001)], occurring at a median time of two days after switch to G-CSF. Clinically relevant adverse events were bone pain (n = 8) and large pleural effusion (n = 1). It was estimated that sequential GM-CSF/G-CSF was cost-effective compared with G-CSF alone [cost-savings of $1311/patient ($41,952/study), 2007 Red Book Average Wholesale Price]. In summary, it was demonstrated that sequential administration of GM-CSF/G-CSF post-MA-alloSCT was safe, cost-effective and resulted in prompt myeloid engraftment.

Characterization of Pleurotus djamor neohaplonts recovered by production of protoplasts and chemical dedikaryotization.

Production of hybrid strains is accomplished by mating monosporic isolates or neohaplonts, obtained either by chemical dedikaryotization or by production of protoplast. However, differences in growth rate among recovered neohaplonts have been reported. The presence of phenotypic and genetic changes among the neohaplonts recovered either by chemical dedikaryotization or by production of protoplast, was evaluated by measuring growth and morphology, and by molecular characterization using six ISSR markers to identify polymorphisms. Neohaplonts recovered by both methods presented variation in growth rate depending on their compatibility type and recovery method. Using ISSR markers, 59.2% polymorphism was established. Neohaplonts recovered by both monokaryotization procedures presented differences in growth rate and polymorphism.

Cutaneous toxoplasmosis histologically mimicking graft-versus-host disease.

The dermatology service is frequently consulted to assess cutaneous eruptions after hematopoietic stem cell transplantation. We describe a case of cutaneous toxoplasmosis in a stem cell transplant patient where toxoplasmosis trophozoites elicited a reaction pattern mimicking an interface dermatitis. At first blush, these findings may be misinterpreted as either a reaction to a drug or graft-versus-host disease. We hope that this case will prove helpful for dermatopathologists in asserting the correct diagnosis of cutaneous toxoplasmosis-if left untreated or treated incorrectly, this disease has a dismal prognosis.

[Use of ITS and ISSR markers in the molecular characterisation of Pleurotus djamor hybrid strains]. / Utilización de marcadores ITS e ISSR para la caracterización molecular de cepas híbridas de Pleurotus djamor.

BACKGROUND: Molecular characterisation of wild type Pleurotus species is important for germplasm conservation and its further use for genetic improvement. No molecular studies have been performed with monokaryons used for producing hybrid strains, either with the reconstituted strains obtained by pairing those monokaryons. The molecular characterisation of parental dikaryons, hybrid, and reconstituted strains as well as monokaryotic strains, is therefore of utmost importance. AIMS: To carry out the molecular identification of Pleurotus djamor strains, i.e. dikaryotic wild type strains, hybrid strains, and the monokaryotic strains used for the hybrid formation. METHODS: Five wild type strains of P. djamor from different states in Mexico were collected and molecularly identified by sequencing the ITS1-5.8-ITS2 region using ITS1 and ITS4 universal oligonucleotides. Four hybrid strains were obtained by pairing neohaplonts of two wild type strains selected. Six ISSR markers were used for the molecular characterisation of monokaryotic and dikaryotic strains. RESULTS: Using the ITS markers, an amplified product of 700bp was obtained in five wild type strains, with a 99-100% similarity with P. djamor. A total of 95 fragments were obtained using the ISSR markers, with 99% of polymorphism. CONCLUSIONS: Wild type strains were identified as P. djamor, and were clearly grouped with Mexican strains from other states of Mexico. ISSR markers allowed the generation of polymorphic bands in monokaryotic and dikaryotic strains, splitting both types of strains. The high degree of polymorphism indicates the genetic diversity of P. djamor, an advantage in mushroom production and in the improving of the species.

Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia.

PURPOSE: Myeloablative allogeneic stem cell transplantation (SCT) has been successful in the treatment of childhood acute myeloid leukemia (AML), but may be associated with significant toxicity and recurrent disease. Reduced-intensity allogeneic SCT may offer a less toxic approach to patients with AML. Targeted immunotherapy with gemtuzumab ozogamicin has been shown to be safe, well tolerated in children, and, as a single agent, gemtuzumab ozogamicin has induced responses in 30% of patients with recurrent CD33+ AML. There are no safety data with gemtuzumab ozogamicin post allogeneic SCT in children. Therefore, we explored the feasibility and toxicity of targeted immunotherapy following reduced-intensity allogeneic SCT in children with CD33+ AML. EXPERIMENTAL DESIGN: Eight patients with CD33+ AML received a reduced-intensity allogeneic SCT following fludarabine 30 mg/m2 for 6 days and busulfan 3.2 mg/kg (<4 years, 4 mg/kg/d) for 2 days. Donor sources included six 6/6 HLA-matched related peripheral blood stem cells, one 6/6 sibling cord blood, and one 4/6 unrelated cord blood. RESULTS: Day 30 and day 60 donor chimerisms in seven of eight evaluable patients were 96 +/- 2% (n = 7) and 94 +/- 3% (n = 6), respectively. Five of six patients (too early for one patient) received two doses of gemtuzumab ozogamicin and one patient received only one dose. After each dose, all patients developed grade 4 neutropenia, with recovery on median days 16 and 13, respectively, after dose 1 and dose 2. Grade 4 thrombocytopenia was only observed in 2 of 11 gemtuzumab ozogamicin courses. No patients have developed dose-limiting toxicity secondary to gemtuzumab ozogamicin. CONCLUSIONS: The administration of gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with average risk AML is feasible and well tolerated with minimal toxicity. The maximal tolerated dose has yet to be determined for gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with CD33+ AML. Additional studies in a larger group of patients will be required to adequately assess the safety of this approach.

Effect of 6-nonadecyl salicylic acid and its methyl ester on the induction of micronuclei in polychromatic erythrocytes in mouse peripheral blood.

The bark of Amphipterygium adstringens is widely used in the traditional Mexican medicine for treating ailments such as gastric ulcers, gastritis and stomach cancer. The 6-nonadecyl salicylic acid (anacardic acid) was isolated from the bark of this species. In previous papers have been informed that the anacardic acids possess anti-tumour, antimicrobial, antiacne, antibacterial and many others medicinal properties. Now we describe cytotoxic and genotoxic effects of this compound and its methyl ester. The cytotoxic and genotoxic effects of 6-nonadecyl salicylic acid (6NDSA) and its methyl ester (ME6NDSA) on CD1 male mice were determined with micronucleus assay at 24, 48 and 72h after oral administration of doses of 0.75, 2.5, 5.0 and 10.0mg/kg. Peripheral blood samples were drawn from the caudal vein and analyzed by Giemsa-stained technique. The results obtained showed that the ratios of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) in mice treated with 10mg/kg of 6NDSA were statistically lower after 24h compared with its negative control animals, and that after 72h, PCE/NCE ratios were reduced in animals treated with 6NDSA at all tested dose levels. The methyl ester ME6NDSA showed no such cytotoxic activity. Neither of the test compounds increased the frequency of micronucleated polychromatic erythrocytes from which it appears that administration of 6NDSA and ME6NDSA may not lead to chromosome damage at the evaluated doses.

Tumor lysis syndrome: pathophysiology, definition, and alternative treatment approaches.

Tumor lysis syndrome (TLS), a life threatening metabolic syndrome seen in malignancies with high tumor burden, is reviewed in this article. The new Cairo and Bishop classification system is discussed as well as the clinical management of this syndrome. Special emphasis is placed on the use of a relatively new agent, rasburicase, as an alternative to allopurinol in the management of TLS-associated hyperuricemia.

Utilización de marcadores ITS e ISSR para la caracterización molecular de cepas híbridas de Pleurotus djamor / Use of ITS and ISSR markers in the molecular characterisation of Pleurotus djamor hybrid strains

Antecedentes. La caracterización molecular de cepas silvestres de Pleurotus es importante para la conservación del germoplasma y su posterior uso en la mejora genética. No se han realizado estudios moleculares con los monocariontes utilizados para la producción de cepas híbridas, ni de las cepas reconstituidas obtenidas al aparear tales monocariontes. Por consiguiente, la caracterización molecular de cepas dicarióticas parentales, híbridas y reconstituidas, así como de cepas monocarióticas, es de suma importancia. Objetivos. Caracterizar molecularmente cepas dicarióticas silvestres e híbridas, así como cepas monocarióticas de Pleurotus djamor. Métodos. Se recolectaron cinco cepas silvestres de P. djamor en diferentes estados de México y se identificaron molecularmente mediante la secuenciación de la región ITS1-5.8-ITS2 con los oligonucleótidos universales ITS1 e ITS4. Se seleccionaron dos cepas silvestres y se generaron cuatro cepas híbridas por apareamiento de neohaplontes compatibles. Para la caracterización molecular de las cepas monocarióticas y dicarióticas seleccionadas y producidas se utilizaron seis marcadores ISSR. Resultados. Con los marcadores ITS se obtuvo un producto de amplificación de 700 pb en las cinco cepas silvestres con una similitud del 99-100% con la especie P. djamor. Con los marcadores ISSR se obtuvieron un total de 95 fragmentos con un 99% de polimorfismo. Conclusiones. Las cepas silvestres se identificaron como P. djamor. Los marcadores ISSR generaron bandas polimórficas en las cepas monocarióticas y dicarióticas, y separaron ambos tipos de cepas. El alto grado de polimorfismo indica la diversidad genética de P. djamor, una ventaja para la producción de hongos y para la mejora de la especie (AU)

Background. Molecular characterisation of wild type Pleurotus species is important for germplasm conservation and its further use for genetic improvement. No molecular studies have been performed with monokaryons used for producing hybrid strains, either with the reconstituted strains obtained by pairing those monokaryons. The molecular characterisation of parental dikaryons, hybrid, and reconstituted strains as well as monokaryotic strains, is therefore of utmost importance. Aims. To carry out the molecular identification of Pleurotus djamor strains, i.e. dikaryotic wild type strains, hybrid strains, and the monokaryotic strains used for the hybrid formation. Methods. Five wild type strains of P. djamor from different states in Mexico were collected and molecularly identified by sequencing the ITS1-5.8-ITS2 region using ITS1 and ITS4 universal oligonucleotides. Four hybrid strains were obtained by pairing neohaplonts of two wild type strains selected. Six ISSR markers were used for the molecular characterisation of monokaryotic and dikaryotic strains. Results. Using the ITS markers, an amplified product of 700bp was obtained in five wild type strains, with a 99-100% similarity with P. djamor. A total of 95 fragments were obtained using the ISSR markers, with 99% of polymorphism. Conclusions. Wild type strains were identified as P. djamor, and were clearly grouped with Mexican strains from other states of Mexico. ISSR markers allowed the generation of polymorphic bands in monokaryotic and dikaryotic strains, splitting both types of strains. The high degree of polymorphism indicates the genetic diversity of P. djamor, an advantage in mushroom production and in the improving of the species (AU)

A low incidence of nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplantation recipients.

Hematopoietic stem cell transplantation (HSCT) is being used to treat a wide spectrum of clinical disorders but opportunistic infection remains an important factor determining outcomes for these patients. Nontuberculous mycobacterial (NTM) infections are being reported more frequently in HSCT recipients and the incidence of NTM infections in adult recipients is reported to be 0.4%-4.9%. However, the incidence and severity of NTM infections are less well described in pediatric HSCT recipients. Centers for Disease Control and Prevention guidelines were used to define definite and probable NTM infection among 132 children undergoing 169 HSCT between January 2000 and December 2004 at our institution. NTM infection was diagnosed in 5 of 132 pediatric recipients (3.8%). There were no NTM infections diagnosed in the autologous HSCT recipients and the incidence of NTM in allogeneic HSCT recipients was 6.4% (95% confidence interval, 0.8-11.9). The mean age of the HSCT recipients who developed NTM infections was 8 years (range, 2-19 years); 3 were male and 2 were female. Four conditioning regimens included alemtuzumab and 3 had antithymocyte globulin. Of the 5 patients with NTM infections, 2 met the criteria for definite infection and 3 for probable infection. Of the 2 patients with definite NTM infection, 1 had disseminated disease with Mycobacterium avium complex and the other had Mycobacterium chelonae catheter-related bloodstream infection. The probable NTM infections were 1 skin infection with Mycobacterium kansasii and 2 lower respiratory tract infections with M avium complex. Median time to NTM infection was 115 days (range, 14-269 days) after HSCT. Two patients had graft-versus-host disease at the time of NTM infection. All 5 patients received 3-4 antimycobacterial drugs and all NTM infections resolved. In summary, the incidence of NTM infection in pediatric HSCT recipients appears similar to that described in adult HSCT recipients and the outcome appears to be excellent with the proper antibiotic therapy. The increased use of anti-T cell antibodies appears to be associated with an increased risk of NTM infections in pediatric HSCT recipients. Multicenter studies are needed to identify the risk factors, early diagnostic criteria, and optimal therapy.

Reduced-intensity allogeneic stem cell transplantation in adults and children with malignant and nonmalignant diseases: end of the beginning and future challenges.

During the last 10 years, multiple studies using reduced-intensity (RI) conditioning followed by allogeneic stem cell transplantation (AlloSCT) have been reported in adult and, less so, pediatric recipients. RI AlloSCT allegedly eradicates malignant cells through a graft-versus-leukemia/graft-versus-tumor effect provided by alloreactive donor T lymphocytes, natural killer cells, or both. Various studies have clearly demonstrated a graft-versus-leukemia/graft-versus-tumor effect in hematologic malignancies and solid tumors. Acute short-term toxicity, including infection and organ decompensation after myeloablative conditioning therapy, can result in a significant incidence of early transplant-related mortality. More importantly, long-term late effects-including growth retardation, infertility, and secondary malignancies-are major complications after myeloablative conditioning therapy, especially in vulnerable children, who are more susceptible to these complications. Recent results comparing RI conditioning with myeloablative conditioning followed by HLA-matched sibling AlloSCT have demonstrated a significant reduction in use of blood products, risk of infections, transplant-related mortality, length of hospitalization, and feasibility of conditioning therapy in outpatient settings. Despite the success of RI AlloSCT, large prospective randomized multicenter studies are necessary to define the appropriate patient population, optimal conditioning regimens and pretransplantation immunosuppression, role of donor lymphocyte infusions, duration of hospitalization, overall survival, cost-benefit ratio, and differences in long-term effects to evaluate the role of RI AlloSCT more fully. We review the recent experience of RI AlloSCT in adults and children with both malignant and nonmalignant diseases and discuss the challenges for the future.

A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients.

Tacrolimus (FK506)/mycophenolate mofetil (MMF) has been demonstrated to be an effective salvage therapy for steroid-resistant chronic graft-versus-host disease (GVHD), but its effectiveness as prophylaxis for acute GVHD (aGVHD) is unknown. We investigated the safety and efficacy of FK506/MMF in preventing aGVHD and sparing the use of methotrexate and methylprednisolone in childhood and adolescent allogeneic stem cell transplant (AlloSCT) recipients. Thirty-four childhood and adolescent patients (median age, 7 years; range, 0.5-21 years; 24 males and 10 females) undergoing 37 AlloSCTs for malignant (n = 22) and nonmalignant (n = 12) disorders received FK506 (0.03 mg/kg/d by continuous intravenous infusion) and MMF (15 mg/kg per dose orally or intravenously twice daily). Stem cell sources included 22 umbilical cord blood donors (21 unrelated and 1 related), 6 related bone marrow donors, and 9 related peripheral blood donors. Malignant diagnoses included 7 acute lymphoblastic leukemias, 3 acute myeloid leukemias, 1 acute promyelocytic leukemia, 2 non-Hodgkin lymphomas, 4 Hodgkin diseases, 3 chronic myeloid leukemias, and 2 neuroblastomas; nonmalignant diagnoses included 2 beta-thalassemias, 1 sickle cell disease, 4 aplastic anemias, 1 Wiskott-Aldrich syndrome, 1 Hurler syndrome, 2 hemophagocytic lymphohistiocytoses, and 1 myelodysplastic syndrome. The probability of developing grade > or =II aGVHD was 45.4% +/- 9.7% (7 related bone marrow/related peripheral blood; 5 umbilical cord blood), and for chronic GVHD it was 38.1% +/- 19.7%. FK506/MMF was well tolerated. Three patients had grade III to IV neurotoxicity (disorientation and leukoencephalopathy); 4 patients developed grade III to IV nephrotoxicity (all received concomitant nephrotoxins). Patients who achieved target mycophenolic acid levels (1.0-3.5 microg/mL) before day +30 had a significantly reduced incidence of developing grade >/=II aGVHD (16.7% +/- 15.2% versus 100%; P <.02). These results suggest that FK506/MMF is well tolerated and may be a safe and effective methotrexate- and methylprednisolone-sparing alternative GVHD prophylaxis regimen after AlloSCT. Further pharmacokinetic and pharmacodynamic studies are ongoing in pediatric and adolescent AlloSCT recipients to define optimal MMF dosing.