Determination of initial i.v. CYA dosage to achieve target AUC values in pediatric hematopoietic stem cell transplant patients.

In solid organ transplantation, CYA dosing is based on the area under the concentration vs time curve (AUC(inf)). This study aimed to develop a guideline for the initial i.v. CYA dose for pediatric hematopoietic SCT (HSCT) patients to achieve the target AUC(inf) recommended in solid organ transplantation. Whole-blood CYA concentrations were determined in 24 patients (0.5-16.9 years) after the first i.v. dose given over 2 h, 1 day before HSCT. The i.v. CYA dose predicted to achieve an AUC(inf) of 4200 microg x h/l was calculated for each patient and expressed as a function of each patient's actual weight and body surface area (BSA). In patients 9 years of age, the mean i.v. CYA dose predicted to achieve the target AUC was 2.6+/-0.94 and 2.1+/-1.21 mg/kg, respectively. When these doses were expressed in terms of BSA, the mean dose was 65+/-23.1 and 68+/-35.0 mg/m(2) in children 9 years of age, respectively. In children 0.5-17 years of age undergoing HSCT, we recommend an initial i.v. CYA dose of 65 mg/m(2) infused over 2 h to achieve an AUC(inf) of approximately 4200 microg x h/l.

Graft-versus-leukemia effect in hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia: significantly lower relapse rate in unrelated transplantations.

To determine graft-versus-leukemia (GVL) effect after hematopoietic stem cell transplantation (HSCT), we studied the outcome of consecutive children with acute lymphoblastic leukemia (ALL) who received fully matched marrow allografts comparing relapse rate post HSCT between matched sibling donor (MSD) and matched unrelated donor (MUD) recipients. Furthermore, we estimated event-free survival (EFS) on the basis of the occurrence of acute graft-versus-host disease (aGVHD). Between 1998 and 2006 we performed 37 fully MSD and 36 fully MUD HSCTs. All patients received identical conditioning regimens with cyclophosphamide/total body irradiation and dual GVHD prophylaxis with cyclosporine (CSA) and methotrexate (MTX). Three-year cumulative incidence of relapse for the MSD and MUD groups were 55.6+/-12.3 and 22.0+/-8.1%, respectively (P=0.03). Three-year EFS according to aGVHD was 32.7+/-12.2% for no aGVHD, 61.2+/-10.0% for grade I-II aGVHD and 66.7+/-11.1% for grade III-IV aGVHD. Three-year EFS and overall survival (OS) were 40.5+/-11.6, 49.1+/-9.5% for the MSD group, and 60.5+/-8.7, 62.3+/-8.4% for the MUD group. In children with ALL receiving dual GVHD prophylaxis, relapse rate is significantly higher among recipients of MSD compared to MUD transplantation, which may in part be attributed to a better GVL effect with the unrelated graft.

Comparative outcome of hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia following cyclophosphamide and total body irradiation or VP16 and total body irradiation conditioning regimens.

To compare the outcome of hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) conditioned with two different regimens: (1) single dose of VP16 (60 mg/kg over 4 h) and total body irradiation (TBI; 1200 cGy, in six fractions) or (2) Cyclophosphamide 50 mg/kg over 1 h daily for 4 days followed by the same dose of TBI. One hundred and seven children with ALL received fully matched HSCT from 1990 to 2003 in the Hospital for Sick Children, Toronto. All received cyclosporin A and a short course of methotrexate for graft-versus-host disease (GVHD) prophylaxis. The VP16 group, there were 36 matched related donor transplants (MRD) and 26 matched unrelated donor transplants (MUD), and in the cyclophosphamide group there were 23 MRD and 22 MUD transplants. Neutrophil engraftment occurred at a median of 18 and 17 days for the VP16/TBI and the CY/TBI groups, respectively. The 3 year event-free survival and overall survival were 47 +/- 7 and 55 +/- 7% for those receiving VP16/TBI, and 51 +/- 8 and 53 +/- 8% for the CY/TBI group. There were no significant differences in the prevalence of acute or chronic GVHD and transplant-related mortality between the two groups. Both VP16/FTBI and CY/FTBI regimen are equally effective regimens.

Allogeneic bone marrow transplantation vs chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic bone marrow transplant (BMT) with an MRD in complete remission (CR)1 is the preferred treatment for children with Philadelphia-positive (Ph(+)) ALL. The role of MUD BMT in CR1 is still controversial. We compared the outcomes of two treatment strategies: BMT using an MRD or MUD vs chemotherapy in children with Ph(+) ALL in CR1. In total, 21 children were treated from 1985 to 2001. In all, 10 received chemotherapy and 11 received allogeneic BMT: four MRD, seven MUD. In the MRD group, one relapsed 12 months after BMT and died; the remaining three are long-term event-free survivors (median follow-up, 6.1 years). In the MUD group four died; the remaining three are long-term event-free survivors (median follow-up, 7.2 years). The 4-year event-free survival (EFS) for the BMT group was 53+/-15%. In the chemotherapy group, seven relapsed after a median period of 12.5 months and three remain in continuous CR (median follow-up, 2.4 years). Four chemotherapy patients received CR2 transplants; all died. The 4-year EFS for the chemotherapy and MUD groups was 33+/-17 and 35.7+/-20%, respectively. This difference was not statistically significant. We continue to support treating children with Ph(+) ALL with MRD BMT in CR1. The effectiveness of MUD BMT vs chemotherapy merits further study.

Outcomes of antiemetic prophylaxis in children undergoing bone marrow transplantation.

A prospective survey of the control of acute and delayed antineoplastic and radiation-induced nausea and vomiting was undertaken in children undergoing bone marrow transplantation (BMT) at The Hospital for Sick Children. Prior administration of antineoplastic agents or irradiation, presence of anticipatory nausea or vomiting prior to starting the conditioning regimen, antiemetic use within 24 h of conditioning, the prescribed antineoplastic and/or radiation ablative regimen, and prescribed antiemetic regimens were recorded. Emetic episodes, dietary intake, administration of conditioning agents and antiemetics, and adverse effects were monitored on each day of the conditioning regimen and for 96 h thereafter. Children older than 3 years of age assessed their nausea on each study day. Twenty-five children were followed for 258 patient days. Children did not vomit or retch on 73% and 43% of patient days, in the acute and delayed phases, respectively. Nausea data were evaluable for 21 children on 200 patient days. Nausea was absent on 55% and 26% of patient days in the acute and delayed phases, respectively. Five children never had an emetic episode during the entire study period. One child was completely free from nausea and vomiting throughout the study period. Antineoplastic and radiation-induced nausea and vomiting can be successfully prevented in the majority of children undergoing BMT. However, effective treatment strategies must be developed in the event of antiemetic failure and for effective prophylaxis in children who cannot tolerate dexamethasone.

Single-centre experience with allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in childhood: similar survival after matched-related and matched-unrelated donor transplants.

Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)-matched related donor (MRD). For these children, BMT from a matched unrelated donor (MUD) represents a therapeutic option. We reviewed the course of 62 children with ALL who received fully matched marrow allografts at our institution between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics were similar in the two groups. The interval from attainment of pre-BMT complete remission to transplant was significantly longer in the MUD group. Conditioning (etoposide/total body irradiation) and graft-versus-host disease (GVHD) prophylaxis regimens were the same for all patients, and all received T cell-replete bone marrow. There was no significant difference in probability of engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a significantly greater incidence of grade II-IV acute GVHD (58% versus 24% in the MRD group; P = 0.02), and demonstrated a trend towards more chronic GVHD (39% versus 15%; P = 0.06). Three years post BMT, the probabilities of transplant-related mortality were 33 +/- 11% and 20 +/- 8% in MUD and MRD groups respectively (P = 0.38); the probabilities of relapse were 28 +/- 12% and 41 +/- 9% respectively (P = 0.19). Lansky or Karnofsky performance scores in event-free survivors were 90-100 in 87% of the MUD group and 83% of the MRD group. With a median follow up of 38 months (range, 3-97), 3-year event-free survival was 49 +/- 11% and 47 +/- 9% in the MUD and MRD BMT groups respectively (P = 0.71). These results suggest that MUD BMT is a valuable therapy for children with ALL in whom BMT is indicated, and underscore the importance of efforts aimed at expediting unrelated donor searches for patients lacking a MRD.

Efficacy and safety of radiologically placed gastrostomy tubes in paediatric haematology/oncology patients.

BACKGROUND: The treatment of malnutrition, which is of great concern in paediatric haematology/oncology patients, is fraught with problems. The goals of our study were to document the complications and assess the weight gain with gastrostomy tubes (G-tubes) in this population. PROCEDURE: Patient data were acquired by retrospective review of all haematology, oncology, and bone marrow transplant (BMT) patients (n = 44) who received radiologically placed G-tubes at our institution over a 4-year period. RESULTS: Forty-four G-tubes were placed (59% peri-BMT). At tube placement, 55% of patients were malnourished and 45% were nourished. Seventy-five percent of patients had the procedure without general anaesthetic. Localized G-tube-site infection was the most common complication (41%). Major complications occurred in 3 patients; 2 patients experienced localized peritonitis, and 1 patient developed a localized collection of pus in the abdominal wall. There were no G-tube-related deaths. At 1 month after the tube insertion, 39% of patients had gained, 54% maintained, and 7% lost weight. At 3 months, 69% had gained, 28% maintained, and 3% lost weight. There was a statistically significant weight gain from the time of the G-tube placement to both 1 month (P < 0.018) and 3 months (P < 0.0001) after G-tube placement. Patients in all diagnosis categories showed improvement from 1 to 3 months. CONCLUSIONS: We conclude that retrograde tube placement is safe and can frequently be done without general anaesthetic and that G-tube feeding effectively reverses malnutrition and prevents weight loss in this patient population.

Retrospective appraisal of busulfan dose adjustment in children.

This report describes and critically appraises our experience with busulfan dose adjustment in children undergoing bone marrow transplant between April 1997 and March 1999. All children received an initial busulfan dose of 40 mg/m2 p.o. or by nasogastric tube. Whole blood samples were obtained 1, 1.5 and 6 h later and analyzed for busulfan content by gas chromatography with electron capture detection. The area under the whole blood busulfan concentration vs time curve (AUC) and an individualized dose which would achieve an AUC of 1300 microM/min were calculated. Mean and median busulfan doses were calculated using actual, ideal and effective body weight and stratified according to age. The relationship between the busulfan concentration at hour 6 and AUC was determined using linear regression. Thirty-nine courses of busulfan were evaluated in 38 patients. A change from the initial busulfan dose was required to achieve the target AUC in 34 courses (87%). Most children >1 to 5 years old required dose increments while most children >5 years old required dose reductions. Obesity did not significantly affect busulfan dose requirements. Busulfan concentrations at 6 h only weakly predicted the AUC achieved (r2 = 0.496; P = 0.001). Based on these findings, we recommend that the initial busulfan dose be assigned according to patient age and actual body weight. We also recommend that busulfan AUC be calculated for children using a four-sample (1, 1.5, 4 and 6 h) limited sampling technique.

Improved survival in severe acquired aplastic anemia of childhood.

Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group.

Telomere shortening in leucocyte subsets of long-term survivors of allogeneic bone marrow transplantation.

Recent studies have demonstrated excessive telomeric shortening in peripheral blood leucocytes of bone marrow transplant (BMT) recipients. This finding has raised concerns about accelerated haemopoietic ageing that might predispose to clonal disorders and late graft failure. We studied the peripheral blood neutrophils and T cells of 14 fully engrafted long-term survivors of BMT. We found that in both neutrophils and T cells there was significant telomere shortening in the recipient (0.6 and 0.5 kb, respectively; P < 0.001 and < 0.04, respectively). We found no relationship between degree of shortening and the nucleated cell dose given at the time of transplant. We also demonstrated significantly longer telomeres in T cells than neutrophils from the same individual (mean 11.6 kb and 10.6 kb, respectively; P=0.0001). We propose mechanisms to account for these observations. The replicative stress that causes this telomere shortening does not necessarily occur at the level of the most primitive haemopoietic stem cell.

Myasthenia gravis and polymyositis as manifestations of chronic graft-versus-host-disease.

Myasthenia gravis and polymyositis are each a rare manifestation of immune dysregulation in chronic graft-versus-host disease (cGVHD). We report a 4-year-old boy with idiopathic acquired aplastic anemia who developed myasthenia gravis 22 months and polymyositis 69 months after an allogeneic BMT (5/6 matched, MLC-nonreactive). The occurrence of both syndromes in one patient is unique. Autoimmune dysfunction may be associated with the development of cGVHD as demonstrated by the high incidence of prior aplastic anemia in BMT patients presenting with myasthenia gravis and polymyositis. Recognition of these neurologic manifestations is important in the diagnosis and treatment of cGVHD.

Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group.

Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group was formed to evaluate the effectiveness and toxicity of BMT. Effectiveness was defined as engrafted survival with continuing cognitive development. Fifty-four patients deficient in leukocyte alpha-L-iduronidase enzyme activity (median age, 1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sibling (GIS) or HLA-haploidentical related (HIR) donors between September 16, 1983 and July 14, 1995; all children were included in this report. Thirty-nine of 54 patients (72%) engrafted following the first BMT. The probability of grade II to IV acute graft-versus-host disease (GVHD) at 100 days was 32% for GIS and 55% for HIR patients. The probability of extensive chronic GVHD was 0% for GIS and 24% for HIR patients. The actuarial probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children transplanted before 24 months had a mean baseline MDI of 78, while those transplanted after 24 months had a mean baseline MDI of 63 (P = . 0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients transplanted before 24 months of age, nine demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients transplanted after 24 months of age, only three showed developmental trajectories that were normal or somewhat slower than normal (P = .01). For children with a baseline MDI greater than 70, there was a significant correlation between the MDI at follow-up study and leukocyte alpha-L-iduronidase enzyme activity (P = .02). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte alpha-L-iduronidase enzyme activity. Children who developed acute GVHD of grade II or worse had significantly poorer cognitive outcomes (P < .009). No difference in the post-BMT MDI was observed between patients whose preparative therapies did (n = 10; radiation dose, 300 to 1,400 cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients, particularly those less than 24 months of age with a baseline MDI greater than 70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successful BMT from a related donor with homozygous normal enzyme activity.

Efficacy of amlodipine in pediatric bone marrow transplant patients.

The calcium antagonist amlodipine may have the potential for expanded use in children owing to its physiochemistry and pharmacokinetic profile that facilitates once-daily dosing in a liquid formulation. Its safety and efficacy have not been previously evaluated in children. A retrospective analysis of 15 pediatric bone marrow transplant patients who had amlodipine incorporated into their antihypertensive drug regimen reveals significantly lower blood pressure as compared with baseline therapy (123.5+/-2.1 mmHg and 117.2+/-2.2 mmHg, systolic blood pressure before and during amlodipine, P<0.05; 81.5+/-1.8 mmHg and 75.5+/-2.6 mmHg, diastolic blood pressure before and during amlodipine, P<0.05). Amlodipine provided improved blood pressure control in this cohort and may provide a valuable pharmacologic alternative for treatment of pediatric hypertension.

Immunoablation does not delay the neurologic progression of X-linked adrenoleukodystrophy.

We report the results of a near total myeloablation in preparation for bone marrow transplantation in a boy with minimal symptoms of X-linked adrenoleukodystrophy. Severe cerebral X-linked adrenoleukodystrophy developed in the patient after failure of bone marrow transplantation. This experience suggests that immunotherapy alone is not responsible for the improvement observed in some patients with X-ALD after BMT.

An improved limited sampling method for individualised busulphan dosing in bone marrow transplantation in children.

Busulphan (BU) pharmacokinetic (PK) studies in children undergoing bone marrow transplantation suggest that individual BU dosing may be necessary to optimise BU systemic exposure. Optimising BU systemic exposure may improve outcome and decrease toxicity in BMT. Because of practical limitations in obtaining blood from children and for financial reasons, a limited sampling method (LSM) is needed. However, such methods for BU have not been validated in children. In the present study, we individualized oral BU dosing in 10 children to target an area under the curve of BU (BU AUC) of 900-1400 microM/min based on BU AUC(0-infinity) calculated from nine serum BU concentrations performed after a BU test dose of 40 mg/m2. We validated a LSM using 3 BU concentrations to determine AUC. Six of nine patients studied (one patient non-evaluable), required their doses modified (3, lower; 3, higher). The mean percent dose change was 26.2% (range -33.3% to +45.3%). Our three sample LSM BU AUC(0-infinity) (1098 +/- 344, mean +/- 1 s.d.) correlated highly with our nine sample BU AUC(0-infinity) (1132 +/- 389, Pearson r = 0.98, P = 0.0001) and was not significantly different by t-test (P = 0.3). The mean percentage difference between the three sample LSM AUCs and the nine sample AUCs in each of our patients was 7.5%, (range -10.99% to +9.4%). Trough levels correlated extremely well with AUC (r = 0.95, P = 0.0001). Individual BU dosing, based on AUC, is necessary in most children to achieve targeted levels of BU therapy. An LSM of three BU concentrations performed at 0.5 h, 1 h and 6 h post-BU test dose closely predicts the AUC calculated from nine sampling points.

Administration of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation in children with acute myelogenous leukemia: a note of caution.

A series of 22 consecutive pediatric patients undergoing ABMT for treatment of primary AML was reviewed in an efficacy analysis of recombinant human granulocytemacrophage colony-stimulating factor (rhGM-CSF). Treatment with at least two cycles of chemotherapy and a standard conditioning regimen of busulfan and cyclophosphamide preceded the marrow infusion. Twelve patients who underwent transplants between 1992 and 1994 received 5.5 micrograms/kg/day rhGM-CSF as part of their transplant protocol. They were compared with 10 patients who underwent transplants between 1989 and 1991 but did not receive rhGM-CSF. Despite containing a significantly higher proportion of patients in first clinical remission at the time of the transplant, the rhGM-CSF-treated group had a significantly higher relapse and poorer overall survival rate after ABMT than the untreated group (36 vs 90%). The rhGM-CSF-treated group tended to have more rapid neutrophil engraftment and shorter hospital stays; however, neither of these trends was statistically significant. To properly determine the role of rhGM-CSF in the survival of pediatric patients undergoing ABMT for treatment of AML, a prospective randomized trial is desirable. Until these data are available, the current analysis suggests that particular caution is indicated with the use of this drug in this group of patients.

Response to measles, mumps and rubella vaccine in paediatric bone marrow transplant recipients.

Bone marrow transplant (BMT) recipients are routinely reimmmunized with the childhood vaccine series after transplantation excluding the live attenuated vaccines. In this study, the clinical and serologic responses to measles, mumps and rubella (MMR) vaccine in children after BMT was assessed. Twenty-two BMT recipients were vaccinated with MMR II (MSD). All were at least 2 years post-BMT and without GVHD. Their underlying conditions were leukemia (11), aplastic or Fanconi's anemia (7), thalassemia (3) and metabolic disease (1). All were allogeneic transplants with matched related donors. The mean age at transplantation was 6.9 years. There were no reported adverse effects of the vaccination. Antibody status for MMR was determined using commercial assays (IFA and ELISA) on paired specimens. The mean interval between transplantation and vaccination was 48 months. Pre-vaccination, no BMT recipient was sero-positive for all three, but 23% were positive for measles, 31% for mumps and 14% for rubella. Post-vaccination, 68% of BMT recipients were sero-positive for all three, with 77% for measles, 87% for mumps and 91% for rubella. Therefore, MMR vaccination at 2 years or later after BMT in paediatric recipients without GVHD was safe and significantly increased the proportion sero-positive for MMR.

Hepatotoxicity of 6-mercaptopurine in childhood acute lymphocytic leukemia: pharmacokinetic characteristics.

Treatment with 6-mercaptopurine (6MP) is associated with adverse gastrointestinal (GI) and hepatic effects. Four patients, ages 6.9 +/- 2.6 (mean +/- S.D.) years, with acute lymphocytic leukemia (ALL) on maintenance chemotherapy including 6MP, developed nausea, vomiting, abdominal pain, elevated liver enzymes, and hyperbilirubinemia after 1.4 +/- 1.0 (range 0.5-2) years. Liver biopsy in 1 patient was suggestive of drug-induced intrahepatic cholestatis. Symptoms resolved and liver function returned to normal after discontinuation of 6MP. Pharmacokinetic data of the symptomatic patients were compared with those of 25 ALL patients on the same protocol but without GI symptoms or hepatotoxicity. Levels of 6-thioguanine nucleotides (6-TGN) and the methylated metabolites of 6MP in red blood cells of the patients with hepatotoxicity, were not significantly different when compared to patients without hepatotoxicity, suggesting similar absorption of 6MP in both groups. Time to achieve peak 6MP levels was significantly longer in the symptomatic patients compared to the asymptomatic patients (P = 0.005). Peak levels and standardized concentration versus time curve (AUC) per 1 mg of 6MP per m2 of body surface area were significantly lower in the patients with hepatotoxicity (P = 0.016; P = 0.037, respectively). A significant correlation between peak 6MP levels and standardized AUC (r = 0.729, P < 0.0001) was found. These results suggest accumulation of 6MP and its metabolites in the liver of the patients with GI symptoms, leading to hepatotoxicity.

Unexpected complications after bone marrow transplantation in transfusion-dependent children.

Ten patients on transfusion-chelation programs were treated with bone marrow transplantation (BMT). The busulfan-cyclophosphamide conditioning regimen was inadequate in the 6 beta thalassemia major patients, resulting in marrow rejection problems for 3. Post BMT one patient remains with thalassemia major and two have mixed chimerism with a clinical status of thalassemia intermedia. Three patients have thalassemia minor from their donors, but one required a second BMT to achieve this state. Two of the four Diamond Blackfan Syndrome patients died of BMT-related complications. Two achieved normal hematopoiesis, one at the price of chronic graft vs host disease. Because of the excellent results of iron chelation in our patients, we question whether such patients with access to the state of the art transfusion-chelation programs should continue to be transplanted. This situation requires continuing evaluation.