Allogeneic hematopoietic cell transplantation for neuroblastoma: the CIBMTR experience.

Although the role of autologous hematopoietic cell transplantation (auto-HCT) is well established in neuroblastoma (NBL), the role of allogeneic HCT (allo-HCT) is controversial. The Center for International Blood and Marrow Transplant Research conducted a retrospective review of 143 allo-HCT for NBL reported in 1990-2007. Patients were categorized into two different groups: those who had not (Group 1) and had (Group 2) undergone a prior auto-HCT (n=46 and 97, respectively). One-year and five-year OS were 59% and 29% for Group 1 and 50% and 7% for Group 2, respectively. Among donor types, disease-free survival (DFS) and OS were significantly lower for unrelated transplants at 1 and 3 years but not at 5 years post HCT. Patients in CR or very good partial response (VGPR) at transplant had lower relapse rates and better DFS and OS, compared with those not in CR or VGPR. Our analysis indicates that allo-HCT can cure some neuroblastoma patients, with lower relapse rates and improved survival in patients without a history of prior auto-HCT as compared with those patients who had previously undergone auto-HCT. Although the data do not address why either strategy was chosen for patients, allo-HCT after a prior auto-HCT appears to offer minimal benefit. Disease recurrence remains the most common cause of treatment failure.

A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children's Oncology Group study ANBL00P1.

Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children's Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8 ± 9.6% and 59.2 ± 9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.

Liver transplantation followed by allogeneic hematopoietic stem cell transplantation for atypical mevalonic aciduria.

Mevalonic aciduria because of mutations of the gene for mevalonate kinase causes limited synthesis of isoprenoids, the effects of which are widespread. The outcome for affected children is poor. A child with severe multisystem manifestations underwent orthotopic liver transplantation at age 50 months for the indication of end-stage liver disease. This procedure corrected liver function and eliminated portal hypertension, and the patient showed substantial improvement in neurological function. However, autoinflammatory episodes continued unabated until hematopoietic stem cell transplantation was performed at 80 months. Through this complex therapy, the patient now enjoys a high quality of life without significant disability.

Treatment of Fanconi anemia patients using fludarabine and low-dose TBI, followed by unrelated donor hematopoietic cell transplantation.

A nonmyeloablative conditioning regimen consisting of fludarabine (FLU) and 2 Gy TBI has been used extensively and with substantial engraftment success without promoting excessive nonrelapse mortality in medically infirm patients requiring hematopoietic cell transplantation. In this paper, we studied this same low-toxicity regimen as a means of promoting engraftment of unrelated donor hematopoietic cell transplantation in patients with Fanconi anemia (FA). All patients tolerated the regimen well with no mucositis or other severe toxicities. Of six patients transplanted, five achieved stable mixed or full donor chimerism. Acute and chronic GVHD occurred in four and three patients, respectively. Three patients are alive and well at a median of 45.9 (range, 20.9-68.1) months after transplant. In summary, this FLU-based regimen facilitates stable engraftment of unrelated PBSCs, but is associated with significant chronic GVHD.

Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant.

We studied the pharmacokinetic (PK) profile of single daily dose i.v. BU in children who underwent reduced-intensity conditioning (RIC) transplantation. A cohort of 19 patients < or =4 years of age (group 1) and 33 patients >4 years (group 2) was studied. Patients received a BU test dose for PK studies, followed by two treatment doses adjusted to target an area under the curve (AUC) of 4000 microM min per day. Patients in group 1 attained a lower AUC as compared to group 2 (3568 vs 4035 microM min). In group 1, 67% patients and in group 2, 84% patients achieved AUC within the targeted range. Stable donor chimerism was achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a second transplantation because of graft failure. Because of the concern that a low AUC adversely affected outcomes, a second cohort of 23 patients followed a modified protocol with a targeted AUC of 5000 microM min. A higher AUC was attained (4825 microM min). Stable donor chimerism was achieved in 91% of patients. Our results show that RIC regimens using two single daily doses of i.v. BU are effective in children, but a targeted AUC of 5000 microM min is recommended.

Weight loss and reduced body mass index: a critical issue in children with multiorgan chronic graft-versus-host disease.

Weight loss and malnutrition are major problems in patients with chronic graft-versus-host disease (GVHD). In adults, low body mass index (BMI) is a predictor for mortality; however, weight loss and BMI have not been studied in pediatric chronic GVHD. A retrospective study on 18 children with extensive chronic GVHD was completed. Median age at SCT was 12.3 (range 0.6-23) years; age at chronic GVHD diagnosis was 12.5 (1-23) years. Patients with multiorgan involvement had a mean maximal decrease in BMI of 20.9% and most dropped below 10th percentile in expected weight-for-age. This change in BMI not only indicates a significant decrease in weight but often a plateau in stature. In contrast, patients with one organ system involved had a mean maximal decrease in BMI of 5% and did not fall below 10th percentile. All patients with multiorgan involvement required salvage therapy beyond steroids and CSA. Three patients died due to complications of chronic GVHD. Weight loss and malnutrition (as reflected by a decrease in BMI) are clinically significant issues in children with multisystem chronic GVHD. Weight loss is likely another systemic manifestation of the disease and may contribute, along with other factors such as increased immunosuppression and infection, to increased mortality in this group.

Comparison of Tc-99 measurement of glomerular filtration rate vs. calculated creatinine clearance to assess renal function pretransplant in pediatric patients undergoing hematopoietic stem cell transplantation.

We compared the results of Tc-99 evaluation of glomerular filtration rate (GFR) vs. the calculation of the creatinine clearance (CCrC) as a predictor for the development of renal insufficiency in pediatric patients following hematopoietic stem cell transplantation (HSCT). We reviewed 95 consecutive patients receiving autologous (n = 37) or allogeneic (n = 58) HSCT at Children's Memorial Hospital between January, 1995 and February, 1998. Diagnoses included leukemia (n = 43), solid tumor (n = 27), bone marrow failure syndrome (n = 12), non-malignant disease (n = 8), CNS tumors (n = 5) and immunodeficiency (n = 3). Tc-99 GFR was compared with a calculated creatinine clearance derived from the Schwartz formula (CCrC) prior to HSCT. These measures of renal function were compared with the patient's subsequent clinical course to determine if patients who developed renal insufficiency of sufficient magnitude as to require continuous veno-venous hemofiltration (CVVH) or dialysis, could have been identified. Overall comparison of the two methods of evaluation of renal function showed low correlation with values obtained by CCrC, which were consistently higher in most patients (r-value 0.01 in the regression analysis and a p = 0.08 95% CI -24.15 to 1.48). When stratified for age, correlation between the two methods was excellent only in children younger than 5 yr of age p = 0.02 95%, CI 0.032-0.49). Eleven patients required therapy with CVVH or dialysis but neither CCrC nor Tc-99 GFR prior to transplant predicted this event. Patients who received TBI were statistically more prone to develop renal insufficiency than those without TBI (p < 0.0001, 95% CI 0.25-0.008). Neither the Tc-99 GFR nor the CCrC was predictive of the development of renal insufficiency in HSCT patients as the majority of patients who required dialysis had normal Tc-99 GFR prior to transplant. The characteristics found in the patients who developed renal insufficiency and required dialysis include: the use of total body irradiation as part of the transplant-conditioning regimen (p < 0.0001) and the use of continuous infusion CSA (p = 0.04).

Wilms' tumor 1 (WT1) gene in hematopoiesis: a surrogate marker of cell proliferation as a possible mechanism of action?

BACKGROUND: Wilms' tumor 1 (WT1) gene expression is seen in a significant number of cases of human neoplasia; however, the mechanism of action remains to be clarified. We hypothesized that WT1 gene is a surrogate marker of proliferation in normal hematopoietic cells and leukemias. While we and others have recognized its value as a tool for the detection of minimal residual disease (MRD), the objective of this study was to confirm our hypothesis regarding normal. METHODS: Samples from healthy donors (n=16) and UC blood (n=9) were cultured in Methocult for 21 days. Colonies were analyzed on days 7, 14 and 21 by RT-PCR for WT1 gene expression. Our positive controls were samples from patients with leukemia (n=91). Negative controls were from normal volunteers without stimulation (n=26). RESULTS: Results showed a statistically significant difference (P<0.0001) between cultured groups, with the highest level of WT1 gene expression in the positive controls and on day 14, when cells are at their maximal proliferation. DISCUSSION: In conclusion, WT1 gene expression in the proliferating colonies was highest on day 14, although less than in leukemia samples, confirming our hypothesis that WT1 gene is a surrogate marker of proliferation, not only in leukemogenesis but also, to a lesser degree, in normal cell proliferation.

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

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.

Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia.

Acute lymphocytic leukemia (ALL) is a common indication for hematopoietic stem cell transplantation (HSCT) in children. Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased GVHD potential. Publications describing outcomes of children with leukemia who underwent UCB transplants have compared them to those having received unrelated donor marrow transplants. Results are similar. We compared our outcomes using UCB vs allogeneic-related hematopoietic stem cells in pediatric ALL patients since 1992. A total of 49 patients were analyzed. All patients were either in CR1 with high-risk features (n=21) or in CR2 (n=28) with initial remission less than 36 months. Patients received myeloablation with fractionated total body irradiation, cyclophosphamide, and etoposide and GVHD prophylaxis with cyclosporine and methotrexate. Antithymocyte globulin was added for UCB recipients to address the HLA differences. In all, 23 patients underwent allogeneic -related HSCT and 26 underwent UCB transplantation. Other than increased time to engraftment for UCB recipients, results are equivalent. The 3-year overall survival is 64% and 3-year event-free survival is 60% for both groups. Rates of GVHD and transplant-related mortality are also equivalent. UCB is a reasonable option for children with ALL who are referred for HSCT.

Platelet chimerism by polymerase chain reaction (PCR) utilizing variable number of tandem repeats (VNTR) in allogeneic stem cell transplant in children: a new novel approach to full chimerism analysis.

Evaluation of chimerism following allogeneic transplantation has been performed traditionally focusing on two cellular compartments, namely lymphoid and myeloid. However, none has been described so far to evaluate platelet chimerism. In order to achieve full chimerism in all three cellular compartments, we prospectively obtained 138 samples of peripheral blood in 55 patients at different post transplant periods following allogeneic hematopoietic transplantation. Evaluation of chimerism was performed utilizing tests of variable number of tandem repeat (VNTR) and sex determination by quantitative polymerase chain reaction (PCR). Tests for platelet chimerism using platelet-rich plasma were simultaneously analyzed with samples for T-cell lymphoid and myeloid compartments. Complete donor chimerism was noted in 49 of 55 patients (89%), while the remaining six have split chimerism ranging from 34 to 98%. There is significant difference (P=0.0004) between the percentages of donor DNA in all three cellular compartments comparing the means+/-s.e.m. (myeloid 95.60+/-0.9, T-cell lymphocytes 87.6+/-1.9, and the platelets 90.8+/-1.5); however, comparison between the medians is not statistically significant. This study represents an additional step towards achieving full chimerism and the observation may help reduce the number of unnecessary platelet transfusions once chimerism is noted in that cellular compartment.

Rapid immune reconstitution following autologous hematopoietic stem cell transplantation in children: a single institution experience.

In this retrospective study, we review the immune reconstitution of children undergoing autologous hematopoietic stem cell transplantation. A total of 125 patients underwent autologous transplantation between 1992 and 2000. The report includes data on 58 patients. Data were not available on the remaining patients who either died before testing or data were not obtained. The parameters evaluated include: (a) immunophenotype by flow cytometry to quantify lymphocyte subpopulations (b) mitogen stimulation assays, and (c) quantitative immunoglobulins. The analysis reveals that CD3+ cells did not reach the normal range during the first year post-transplant. The median percentage of CD4+ cells was below normal up to 6 months post-transplant, while the absolute number remain low throughout the first year. The CD8+ percentage and absolute numbers remain normal at all times post-transplant. The CD19+ cells were also normal post-transplantation. The mitogen lymphocyte stimulation was normal in 27 out of 31 patients tested after 6 months post-transplant. Our analysis of immune reconstitution shows a similar pattern to previous studies with a faster recovery of the CD4/CD8 ratio, especially in those patients who did not receive TBI. In conclusion, the observed deficiencies are transient and have very little clinical significance because, historically, the rate of serious infections is low despite prolonged immune suppression. The recovery post-autologous transplant is fast.

Evaluation of mixed hematopoietic chimerism in pediatric patients with leukemia after allogeneic stem cell transplantation by quantitative PCR analysis of variable number of tandem repeat and testis determination gene.

In order to monitor the clinical outcome of pediatric patients with leukemia following allogeneic hematopoietic transplantation, tests of variable number of tandem repeat (VNTR) and sex determination by quantitative polymerase chain reaction (PCR) were performed. PCR results combined with the blast counts from 21 leukemia patients were analyzed. Complete chimerism (100% donor cells) was found in 15 cases with remission, and incomplete chimerism in six cases with relapse. In the majority of cases, complete chimerism was always associated with no detectable blasts, while blasts were often detected in association with incomplete chimerism. There is significant correlation (P<0.0001) between the percentage of donor DNA and blast percentage in these patients. Early detection of incomplete chimerism may therefore predict a poor prognosis. In one patient (case 15), a differing percentage of donor DNA was observed between samples of bone marrow and peripheral blood collected on the same day. This may be due to the fact that allogeneic stem cells proliferate at different rates depending on their environment (bone marrow or peripheral blood). In addition, 100% donor cells found in the peripheral blood may not reflect the number of cells in the bone marrow. In case 17, asynchronous engraftment of donor cells was present between the white and red blood cell lineages, indicating that the degree of chimerism may not be the same in all cell lineages. At the time of this report, the significance of this observation is unknown and needs further investigation.

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Developing a pediatric outpatient transplantation program. The Children's Memorial Hospital experience.

We describe the development of a pediatric outpatient transplant program and our initial experience with autologous and allogeneic transplants performed partially or completely in the outpatient setting. Forty-eight autologous and seven allogeneic transplants have been performed in our institution in the outpatient setting between June 1994 and July 2000. The ablation used for the autologous outpatient transplants was VP-16 1000 mg/m2/ day as a continuous infusion for 2 days and Carboplatinum 667mg/m2/day for 2 days. The autologous inpatient transplants received Thio-tepa 300-mg/ m2per day x 3 days and cyclophosphamide 60 mg/kg/day for 4 days. For those patients who received an immune-ablative allogeneic outpatient transplant, the regimen consisted of Fludarabine 30 mg/m2/day for 6 days, followed by busulfan for children less than five years of age 1 mg/kg/dose x 8 doses and for those five years and older 0.8 mg/kg/dose x 8 doses, followed by ATG 40mg/kg/day x 4 days. Engraftment was complete in all transplants achieving an ANC >500 for the outpatient transplant in 15 days (10-35) vs. the inpatient in 15 days (14-58). This was not statistically significant. They achieved un-sustained platelets >20.0 by day 19 (14-58) for the outpatients and day 32 10-64) for the inpatient. The allogeneic immune ablative transplants were considered engrafted when their VNTRs were greater that 30% which was achieved at a median of 13 days (10-27). The economic data showed a statistically significant decrease in charges and direct costs between the outpatient (median charges $30 775, direct costs $8 389) and the inpatient (median charges $99 838, direct costs $42 757) transplants (p0.001). There was no difference in morbidity and mortality between the two groups but the use of empiric amphotericin B was markedly decreased in the outpatient transplants. In conclusion it is feasible and less costly to perform autologous hematopoietic stem cell transplants in the outpatient setting with no increase in morbidity and mortality. For the allogeneic transplants there is not yet enough data to establish a similar conclusion.

Expansion of megakaryocyte precursors and stem cells from umbilical cord blood CD34+ cells in collagen and liquid culture media.

Umbilical cord blood (UCB) is now commonly used as a source of stem cells for hematopoietic reconstitution following myeloablative therapy in patients with a variety of diseases. Although UCB is a rich source of stem cells, platelet engraftment occurs at a median of 71 days which is significantly prolonged compared to allogeneic bone marrow. The number of megakaryocyte (MK) precursors in stem cell harvests appears to correlate inversely with the time to platelet engraftment. In an effort to increase the number of platelet precursors, we cultured CD34-selected cord blood mononuclear cells (MNC) in serum-free collagen medium with numerous cytokine combinations. The cells were cultured with four cytokines: interleukin-3 (IL-3), thrombopoietin (TPO), stem cell factor (SCF), and Flt-3); five cytokines, IL-3, TPO, SCF, Flt-3 plus granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (Epo); or all six cytokines in combination. After 16 days, significant expansion of MK precursors (CD41(+)) and stem cells (CD34(+) and AC133(+) cells) were seen in cells cultured in IL-3, TPO, SCF, and Flt-3 with or without GM-CSF compared to the combinations that contained Epo (p < 0.05). Similar studies were performed using liquid culture medium, and after 14 days the number of MNCs, CD34(+), AC133(+), CD41(+), and CD61(+) cells were higher in the UCB cells cultured in IL-3, TPO, SCF, and Flt-3 compared to those cultured with those four cytokines plus GM-CSF. These results demonstrate that UCB stem cells can be effectively expanded ex vivo and enriched with platelet precursors using TPO, SCF, Flt-3, and IL-3, whereas the addition of Epo and GM-CSF is unnecessary.

Unrelated cord blood transplant experience by the pediatric blood and marrow transplant consortium.

Cord blood (CB) has emerged as a potential source of hematopoietic stem cells for patients who are in need of hematopoietic stem cell transplant (HSCT). The authors analyzed the Pediatric Blood and Marrow Transplant Consortium's (PBMTC) data of consecutive unrelated CB transplants performed during the initial 2 years of using placental blood grafts. From January 1995 to December 1996 PBMTC performed a total of 44 unrelated CB transplant for a variety of diseases consisting of acute leukemias (n = 29), congenital conditions (n = 9), and bone marrow failure (n = 6). There were 15 females and 29 males with median age of 5 years (range 0.4-20.6 years) and median weight of 18.2 kg (range 6.3-70 kg). The median volume of CB units was 80 mL (range 44.5-215 mL) and the median cell dose given was 4.3 x 10(7)/kg of recipient weight (range 1.1-23 x 10(7)/kg). Techniques used for human leukocyte antigen (HLA) matching were serologic typing for class I HLA antigens and high-resolution molecular typing for HLA-DRB1 alleles. HLA disparities were as follows: 4 were 6/6 matches, 21 were 5/6, 15 were 4/6, and 4 were 3/6. Twenty-nine (66%) of CB units were DRB1 matched with recipients. Conditioning regimens consisted of either total body irradiation containing (n = 31) or chemotherapy only (n = 11) regimens. All but 3 patients receive cyclosporine as part of graft vs. host disease (GvHD) prophylaxis in combination with either methotrexate (MTX) or methylprednisolone (Pred). The other 3 patients had FK506 and MTX for GvHD prophylaxis. Myeloid engraftment (absolute neutrophil count > or = 500) occurred at a median of 21 days (range 10-43 days) and platelet > or = 50,000/mm3 was noted at a median of 44 days (range 16-102 days). Eight patients died too early (< day + 28) for evaluation of engraftment (5 for infection, 2 for multiorgan failure, 1 for toxic epidermolysis). The probability of having grade II-IV acute GvHD for all patients was 44 +/- 0.7%. The incidence of a GvHD is similar for 4/6 and 5/6 antigen when DRB1 matched, at 47 and 52%, respectively. Chronic GvHD was noted in 28% of patients surviving > 90 days. The Kaplan-Meier estimate of 4-year event-free survival was 43%. A Cox model for analysis of factors associated with survival was DRB1 matching, p = .001; cell dose, p = .009; and younger age, p = .03. In conclusion, CB transplant offers a good alternative to bone marrow transplant Although GvHD occurs, it is usually of low severity despite the high frequency of multiple HLA antigen mismatches. It also appears that a 4/6 is as good as a 5/6 matched antigen CB unit when DRB1 matched especially in the pediatric setting.

Detection of EBV DNA in the cord blood donor for a patient developing Epstein-Barr virus-associated lymphoproliferative disorder following mismatched unrelated umbilical cord blood transplantation.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorder (PTLD) has been well described as a complication following allogeneic stem cell transplantation but has only recently been reported following umbilical cord blood (UCB) transplant. We report the case of a child transplanted with unrelated mismatched UCB for juvenile chronic myelogenous leukemia (JCML) who developed EBV-associated PTLD, which was confirmed pathologically, 139 days following stem cell infusion. There was no clinical response to reduction of immune suppression, high-dose acyclovir, or alpha interferon. The patient died 160 days after transplantation. EBV was detected by polymerase chain reaction in the cord blood unit used for transplantation. This case demonstrates that EBV-associated PTLD can occur following mismatched unrelated UCB transplant and may be related to transmission of EBV infection by donor lymphocytes.

Treatment of congenital erythropoietic porphyria in children by allogeneic stem cell transplantation: a case report and review of the literature.

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder of porphyrin metabolism in which the genetic defect is the deficiency of uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity and mutilating skin lesions. We describe the case of a 23-month-old boy who was cured of his CEP by a matched-sibling allogeneic bone marrow transplant, and review the published clinical experience regarding transplantation in this disease. He is alive and disease-free 15 months post transplant. All of his disease manifestations except for the erythrodontia have resolved. His UIIIC level and stool and erythrocyte porphyrin metabolites have almost completely corrected. He is the sixth child reported to be cured of this disease by stem cell transplantation, five cases being long-term survivors. If patients with this disease have an HLA-matched sibling, then stem cell transplantation should be strongly considered because this is currently the only known curative therapy.