Low‐dose total‐body irradiation and alemtuzumab‐based reduced‐intensity conditioning regimen results in durable engraftment and correction of clinical disease among children with chronic granulomatous disease

HSCT with MAC is associated with durable donor engraftment for patients with CGD; however, MAC is limited by high rates of RRT. We used a novel RIC regimen with LD‐TBI (200 cGy × two doses), fludarabine (30 mg/m² × three doses), and proximal alemtuzumab (0.5 mg/kg/dose × one dose) and unrelated donor grafts for consecutive patients with high‐risk CGD who were not candidates for MAC at our institution. Among four children with CGD transplanted at our institution, three PBSC recipients are alive with sustained donor engraftment (median follow‐up: two yr) and resolution of pre‐HSCT active infections while one patient with bone marrow graft is alive after graft failure and autologous recovery. RIC may be a curative option for children with high‐risk CGD.     

Safety and feasibility of granulocyte colony‐stimulating factor (G‐CSF) primed bone marrow (BM) using three days of G‐CSF priming as stem cell source for pediatric allogeneic BM transplantation

There are limited data on the optimal dosing and schedule of G‐CSF priming prior to BM harvest. We evaluated the safety and efficacy of three days of G‐CSF of primed BM from related pediatric donors. Forty‐five children were treated. All donors received 5 μg/kg per day of G‐CSF as a single subcutaneous injection for three consecutive days prior to the BM harvest. The median age of the donors was seven yr (range, 0.8–18) and no donor experienced major adverse events related to G‐CSF administration. The median age for the recipients was five yr (0.3–16 yr). Thirty‐five patients had non‐malignant disorders. The median dose of nucleated (TNC) and CD34+, CD3 cells infused per recipient weight was 5.4 × 10⁸/kg (range, 0.61–17), 4.7 × 10⁶/kg (range, 1.6–19), and 43.8 × 10⁶/kg (range, 1.8–95), respectively. All patients achieved neutrophil and platelets engraftment, at a median of 15 (range, 10–22) and 23 days (range, 13–111), respectively. At a median follow up of 60 months (range 12–100), the estimated five yr overall and EFS was 91% and 80%, respectively. Collection of BM following three days of G‐CSF priming from pediatric donors is safe and results in high TNC and CD34+ cell yield.     

TCR α+β+/CD19+ cell–depleted hematopoietic stem cell transplantation for pediatric patients

TCR α⁺β⁺/CD19⁺ cell depletion is an emerging technique for ex vivo graft manipulation in HSCT. We report 20 pediatric patients who underwent TCR α⁺β⁺/CD19⁺ cell–depleted HSCT in four Australian centers. Conditioning regimen was dependent on HSCT indication, which included immunodeficiency (n = 14), Fanconi anemia (n = 3), and acute leukemia (n = 3). Donor sources were haploidentical parent (n = 17), haploidentical sibling (n = 2), or matched unrelated donor (n = 1). Mean cell dose was 8.2 × 10⁸/kg TNC, 12.1 × 10⁶/kg CD34⁺ cells, and 0.4 × 10⁵/kg TCR α⁺β⁺ cells. All patients achieved primary neutrophil and platelet engraftment, with average time to neutrophil engraftment 11 days (range 8‐22) and platelet engraftment 24 days (range 12‐69). TRM at 1 year was 15%. Rate of grade II‐IV aGVHD at 1 year was 20% with no grade III‐IV aGVHD seen. CMV reactivation occurred in 81% of CMV‐positive recipients, with one patient developing CMV disease. Average time to CD4 recovery (>400 × 10⁶/L) was 258 days. Overall survival for the cohort at 5 years was 80%. This report highlights the initial experience of TCR α⁺β⁺/CD19⁺ cell–depleted HSCT in Australian centers, with high rates of engraftment, low rates of aGVHD, and acceptable TRM.     

BK virus encephalitis and end‐stage renal disease in a child with hematopoietic stem cell transplantation

BK virus encephalitis after HSCT is uncommon. Several reports of native kidney BKVN in patients with HSCT, hematologic malignancies, human immunodeficiency virus infection, and non‐renal solid organ transplantation have been described. However, an uncommon combination of BK encephalitis and ESRD of native kidneys secondary to BK virus in a child with HSCT has not been described. We report a 10‐year‐old boy who presented with a gradually rising serum creatinine during treatment for severe autoimmune hemolytic anemia, which he developed 9 months after receiving an allogeneic HSCT for aplastic anemia. There was no proteinuria or hematuria present. Serum BK virus load was 5 × 10⁶ copies/mL. A renal biopsy showed evidence of BKVN. He developed fever, seizures, and confusion, and the (CSF) showed significant presence of the BK virus (1 × 10⁶ copies/mL) along with biochemical evidence of viral encephalitis. Cerebrospinal fluid cultures were negative. Despite significant clinical symptoms and presence of BK virus in CSF, the magnetic resonance brain imaging findings were minimal. With reduction of immunosuppression, there was resolution of BK encephalitis but BKVN remained resistant to multiple anti‐BK virus agents, including leflunomide and cidofovir. He eventually became dialysis‐dependent and, 6 years later, received a renal transplant from his mother. This case illustrates that BK virus in severely immunocompromised HSCT recipient may lead to BK encephalitis and BKVN of native kidneys, even without hemorrhagic cystitis, leading to ESRD. Knowledge of such is important for appropriate timely evaluation and management.     

Haploidentical parental hematopoietic stem cell transplantation in pediatric refractory Langerhans cell histiocytosis

Children with MS‐LCH that fail to respond to conventional chemotherapy have poor outcomes. HSCT represents a potential salvage approach. It has been applied in over 50 cases in recent years. HSCT can achieve greater disease control than chemotherapy, but it carries a high risk of transplant‐related mortality; thus, the haploidentical parental HSCT is used infrequently in pediatric refractory LCH. We report the first successful haploidentical parental HSCT, with no T‐cell depletion, in two girls, aged 26 months and five months, with refractory MS‐LCH. The mothers were donors with 5/6 and 4/6 HLA matches, respectively. The conditioning regimen included busulfan + cyclophosphamide + etoposide + antithymocyte‐globulin ± fludarabine; the GVHD prophylaxis was based on cyclosporine + methotrexate ± mycophenolate‐mofetil ± zenapax. In both cases, the stem cells were sourced from peripheral blood and BM, which included CD34+ cells (13.17 × 10⁶/kg and 40.23 × 10⁶/kg, respectively). These patients survived and showed no signs of disease activity in 54‐ and 44‐month post‐HSCT follow‐ups. Our results indicated that, for patients that fail chemotherapy delivered early in the disease, but do not show organ dysfunction progression, it may be possible to achieve successful haploidentical parental HSCT with a strong myeloablative regimen.     

Successful treatment of non‐Hodgkin's lymphoma using R‐CHOP in a patient with Wiskott–Aldrich syndrome followed by a reduced‐intensity stem cell transplant

WAS is an X‐linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmunity and malignancy. HSCT is the only curative treatment for WAS. Herein, we report the case of a 17‐yr‐old boy with WAS who received an unrelated HSCT while in complete remission of diffuse large B‐cell lymphoma after chemotherapy. Pretransplant conditioning consisted of fludarabine, busulfan, and total body irradiation (4 Gy). GvHD prophylaxis consisted of tacrolimus and short‐course methotrexate. Following HSCT, rapid and stable engraftment was observed. Platelet count gradually increased, and the generalized eczema improved. The patient developed grade II acute GvHD and limited chronic GvHD on days 30 and 210, respectively, which resolved with immunosuppressive treatment. Symptoms caused by the reactivation of human herpes virus‐6, BK virus, and VZV were observed from days 21, 60, and 96, respectively; they were resolved after conservative treatment and acyclovir administration. No other regimen‐related toxicity was observed. Complete donor bone marrow chimerism was achieved one month after transplantation. RIST is an effective therapeutic option for older children with WAS accompanied by malignant lymphoma.     

Unrelated donor cord blood transplantation for non‐malignant disorders in children and adolescents

This study analyzes the data reported to the Korean Cord Blood Registry between 1994 and 2008, involving children and adolescents with non‐malignant diseases. Sixty‐five patients were evaluated in this study: SAA (n = 24), iBMFS, (n = 16), and primary immune deficiency/inherited metabolic disorder (n = 25). The CI of neutrophil recovery was 73.3% on day 42. By day 100, the CI of acute grade II–IV graft‐versus‐host disease was 32.3%. At a median follow‐up of 71 months, five‐yr OS was 50.7%. The survival rate (37.5%) and CI of neutrophil engraftment (37.5%) were lowest in patients with iBMFS. Deaths were mainly due to infection, pulmonary complications, and hemorrhage. In a multivariate analysis, the presence of >3.91 × 10⁵/kg of infused CD34 +  cells was the only factor consistently identified as significantly associated with neutrophil engraftment (p = 0.04) and OS (p = 0.03). UCBT using optimal cell doses appears to be a feasible therapy for non‐malignant diseases in children and adolescents for whom there is no appropriate HLA‐matched related donor. Strategies to reduce transplant‐related toxicities would improve the outcomes of UCBT in non‐malignant diseases.     

Autologous cord blood transplantation for metastatic neuroblastoma

Auto‐SCT is a common approach for metastatic neuroblastoma with the intention to rescue hematopoiesis after megadose chemotherapy. PBSC or BM is the usual stem cell source for auto‐SCT. Auto‐CBT for neuroblastoma has very rarely been performed. Currently, case reports are available for two patients only. We performed 13 auto‐SCTs for high‐risk neuroblastoma from 2007 to 2013, including four cases of metastatic neuroblastoma aged 11–64 months treated with auto‐CBT. All four patients had partial or CR to upfront treatments before auto‐CBT. Nucleated cell dose and CD34+ cell dose infused were 2.8–8.7 × 10⁷/kg and 0.36–3.9 × 10⁵/kg, respectively. Post‐thawed viability was 57–76%. Neutrophil engraftment (>0.5 × 10⁹/L) occurred at 15–33 days, while platelet engraftment occurred at 31–43 days (>20 × 10⁹/L) and 33–65 days (>50 × 10⁹/L) post‐transplant, respectively. There was no severe acute or chronic complication. Three patients survived for 1.9–7.7 yr without evidence of recurrence. One patient relapsed at 16 months post‐transplant and died of progressive disease. Cord blood may be a feasible alternative stem cell source for auto‐SCT in patients with stage 4 neuroblastoma, and outcomes may be improved compared to autologous PBSC or BM transplants.     

High‐dose chemotherapy with autologous stem cell rescue for treatment of retinoblastoma: Report of five cases

RB is a primarily pediatric cancer arising from the retina, initiated by biallelic loss of the RB1 gene. We report five children with bilateral RB (n = 3), extra‐ocular disseminated RB, or disseminated relapsed RB, who were treated with tandem high‐dose chemotherapy and autologous stem cell rescue. All patients received at least 2.2 × 10⁶/kg CD34⁺ (median, 3.9 × 10⁶/kg) cells. The preparative regimen for course 1 was carboplatin, thiotepa, etoposide, and for course 2, CM and melphalan. ANC of at least 0.5 × 10⁹/L occurred at a median of 11 days (range, 10–12) and 15 days (range, 12–16) after the first and second procedure, respectively. Platelet engraftment occurred at a median of 13 days (range, 12–17) and 15 days (range, 14–22) after the first and second procedure, respectively. All of the five patients treated remain alive and disease free at the last follow‐up time, ranging between 21 and 44 months after completion of autologous transplant. Additional therapy was required in one patient, in whom enucleation had to be performed because of early disease relapse, refractory to local therapy. Intensification of chemotherapy with repeated high‐dose chemotherapy and autologous rescue appears an acceptable choice in selected cases with bilateral or extra‐ocular disease, either recurrent or refractory.     

Autoimmune thyroiditis following HLA‐matched sibling hematopoietic stem cell transplantation for Wiskott‐Aldrich syndrome

WAS is a fatal X‐linked combined immunodeficiency syndrome, the only cures for which are HSCT or gene therapy. AID occur in up to 72% of patients with WAS who do not receive HSCT, likely arising secondary to impaired multilineage immune autoregulatory function; AITD is not typically seen. In this article, we describe the case of a male patient who underwent HLA‐matched HSCT for WAS at the age of 5 months, with his sister (a WAS carrier) acting as his donor and subsequently developed AITD 12 months post‐transplant, with marked elevation of antithyroid peroxidase antibody titer. His donor sister was subsequently found to have elevated antithyroid peroxidase antibody titer with increasing trend and normal thyroid function. Although several mechanisms exist by which our patient may have developed AITD, we suggest the transfer of autoreactive donor immune cells as the most plausible explanation.     

Selective T cell‐depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma

Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft‐versus‐NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T‐cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49‐11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T‐cell depletion (CD3/CD19‐depletion=1; TCR‐αβ/CD19‐depletion=4; CD3/CD45RA‐depletion=4; and TCR‐αβ/CD45RA‐depletion=1). Conditioning regimens were fludarabine‐based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 10⁹/L) on median D + 8 (range: D + 5 to D + 14). Early T‐ and NK‐cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor‐chimerism post‐HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T‐cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB.     

Hypocellular acute myeloid leukemia treated with bone marrow transplantation

Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and is extremely rare in childhood. There is still no established treatment for hypocellular AML. We report the case of an 11‐year‐old boy with hypocellular AML who was treated successfully with allogenic bone marrow transplantation (allo‐BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration and biopsy confirmed a diagnosis of hypocellular AML. Although low‐dose cytarabine induced reduction of blasts, it did not lead to complete remission. He subsequently received myeloablative conditioning and allo‐BMT. Graft‐versus‐host disease (GVHD) prophylaxis included short‐course methotrexate and cyclosporine. Neutrophil engraftment (>5 × 10⁸/L) and platelet recovery (>10 × 10¹⁰/L) were achieved on days 13 and 27, respectively. He developed acute GVHD of the skin (grade 2), which responded well to treatment with prednisolone. He has remained in complete remission for 5 years since allo‐BMT. We consider allo‐BMT to be feasible for children with hypocellular AML.     

Successful long‐term hematological and immunological reconstitution by autologous cord blood transplantation combined with post‐transplant immunosuppression in two children with severe aplastic anemia

aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for‐profit cord blood‐banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 10⁷/kg, and 3.8 × 10⁷/kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post‐transplant immunosuppression with cyclosporine for 12 months. They remain disease‐free 6 years post‐transplantation.     

Incidence,risk factors,and outcome of blood stream infections during the first 100 days post‐pediatric allogeneic and autologous hematopoietic stem cell transplantations

Bloodstream infections (BSI) are a frequently observed complication after hematopoietic stem cell transplant (HSCT). Retrospective analysis of clinical and microbiological data during the first 100 days from 302 consecutive pediatric patients who underwent HSCT for a malignant disease at our institute between January 2013 and June 2017. A total of 164 patients underwent autologous and 138 allogeneic HSCT. The overall incidence of BSI was 37% with 92% of infectious episodes occurring during the pre‐engraftment phase. Gram‐positive bacteria (GPB) accounted for 54.6% of the isolated pathogens, gram‐negative bacteria (GNB) for 43.9%, and fungi for 1.4%. Coagulase‐negative staphylococci and Escherichia coli were the most commonly isolated GPB and GNB, respectively. Forty‐five percent of GNB were extended‐spectrum beta‐lactamase producers and 21% were multidrug‐resistant organisms. Fluoroquinolone resistance was 92% and 68%, among GPB and GNB, respectively. Risk factors for BSI in univariate analysis were allogeneic HSCT, delayed time to engraftment more than 12 days, previous BSI before HSCT, and alternative donor. In multivariate analysis, only HSCT type (allogeneic vs autologous P = .03) and previous BSI within 6 months before HSCT (P = .016) were significant. Overall survival at day 100 was 98% and did not differ significantly between patients with and without BSI (P = .76). BSI is common in children undergoing HSCT for malignant diseases. Allogeneic HSCT recipients and previous BSI within 6 months before HSCT are associated with increased risk of post‐transplant BSI. With current supportive measures, BSI does not seem to confer an increased risk for 100‐day mortality.     

Successful treatment with pulse cyclophosphamide of a steroid-refractory hepatitic variant of liver acute graft-vs.-host disease in a child

Kawahara Y, Morimoto A, Masuzawa A, Ikeda T, Hayase T, Kashii Y, Nozaki Y, Kanai N, Momoi MY. Successful treatment with pulse cyclophosphamide of a steroid‐refractory hepatitic variant of liver acute graft‐vs.‐host disease in a child.
Pediatr Transplantation 2012: 00: 000–000. © 2012 John Wiley & Sons A/S. Abstract: A 13‐yr‐old boy with recurrent acute myeloid leukemia underwent HSCT using cells from an unrelated donor who matched all HLA antigens except one. Forty‐two days later, the patient developed a steroid‐refractory hepatitic variant of liver GVHD with peak ALT and T.Bil values of 1406 mU/mL and 10.4 mg/dL, respectively. He was successfully treated with pulse Cy (1000 mg/dose × one day) without a change in chimerism being observed or acquiring an infection. All immunosuppressant therapies could be discontinued 12 months after HSCT. Two yr after HSCT, the patient remains in CR without chronic GVHD. This single case report suggests that pulse Cy may be a promising therapy for steroid‐refractory GVHD, especially hepatitic GVHD, but needs to be further tested in clinical trials.     

Acanthamoeba granulomatous amoebic encephalitis after pediatric hematopoietic stem cell transplant

Acanthamoeba encephalitis is a rare, often fatal condition, particularly after HSCT, with 9 reported cases to date in the world literature. Our case was originally diagnosed with ALL at age 3 years, and after several relapses underwent HSCT at age 9 years. At 17 years of age, he was diagnosed with secondary AML for which he underwent a second allogeneic HSCT. He presented with acute‐onset worsening neurological deficits on day +226 after the second transplant and a post‐mortem diagnosis of Acanthamoeba encephalitis was established, with the aid of the CDC.     

Taste dysfunction in patients undergoing hematopoietic stem cell transplantation: Clinical evaluation in children

The aim of this study was to determine the variability of TD in children undergoing HSCT. Cases were identified as consecutively enrolled children in the period January 2011–January 2013 among patients attending the Paediatric Department of Spedali Civili of Brescia and all candidates to HSCT. The TST was conducted in two phases: identification of threshold values and identification of perceived stimulus intensity. Sixteen sapid solutions with four flavors (sucrose, sodium chloride, citric acid, and quinine hydrochloride) at four different concentrations were administered in a random sequence. The same protocol was administered at different time intervals: before starting the conditioning therapy (T0), during the conditioning therapy (T1) (two times), and every three months (two times) after engraftment post‐HSCT (T2). A p‐value < 0.05 was considered statistically significant. Fifty‐one children (29 female and 22 male, mean age 5.2 ± 0.7 yr) were enrolled. Threshold value means for the four flavors increased during HSCT conditioning therapy (T1) (p < 0.01); intensity of perceived stimulus decreased during HSCT conditioning therapy (p < 0.01). At six months after engraftment (T2), both parameters had returned to starting values (T0). Changes in taste perception in children undergoing HSCT seem to occur especially during the conditioning therapy and resolve in about six months after engraftment post‐HSCT.     

Romiplostim treatment allows for platelet transfusion‐free liver transplantation in pediatric thrombocytopenic patient with primary sclerosing cholangitis

Thrombocytopenia is a major risk factor for cirrhotic liver disease. Patients with thrombocytopenia may have esophageal or gastric varices secondary to portal hypertension, leading to variceal bleeding which exposes the liver to further damage. Here, we present a female pediatric patient with PSC and CD, whose progressive thrombocytopenia was successfully controlled by romiplostim, a TPO receptor agonist. The patient developed bloody diarrhea at four yr of age, and was subsequently diagnosed with PSC and CD when seven yr old. While CD was well‐controlled by immunomodulators, the patient's thrombocytopenia gradually progressed resulting in petechiae (platelet count of 11 × 10⁹/L) when she was 10 yr and four months old. She responded poorly to immunoglobulin and corticosteroids. Weekly subcutaneous injection of romiplostim was therefore initiated, and platelet counts were maintained over at 50 × 10⁹/L. She was able to undergo successful LDLT without platelet transfusion seven months after the initiation of romiplostim. Romiplostim was not required after LDLT with improved platelet counts. This case report suggests that romiplostim may be effective in the treatment of thrombocytopenic children with liver cirrhosis and portal hypertension, and in eliminating the need for platelet transfusion during the peri‐transplant period.     

Defibrotide for the treatment of hepatic veno‐occlusive disease/sinusoidal obstruction syndrome following nontransplant‐associated chemotherapy: Final results from a post hoc analysis of data from an expanded‐access program

1 Background

Hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant‐associated chemotherapy. Following HSCT, VOD/SOS with multi‐organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post‐HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post‐HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded‐access treatment (T‐IND) program. A post hoc analysis of nontransplant‐associated VOD/SOS patients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented.

2 Procedure

Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended).

3 Results

Of the 1,154 patients in the T‐IND, 137 had nontransplant‐associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan–Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan–Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment‐related adverse events occurred in 26.8%.

4 Conclusions

In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan–Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies.     

Hydroxyurea therapy in UK children with sickle cell anaemia: A single‐centre experience

1 Introduction

Despite the demonstrated efficacy of hydroxyurea therapy, children with sickle cell anaemia in the UK are preferentially managed with supportive care or transfusion. Hydroxyurea is reserved for children with severe disease phenotype. This is in contrast to North America and other countries where hydroxyurea is widely used for children of all clinical phenotypes. The conservative UK practice may in part be due to concerns about toxicity, in particular marrow suppression with high doses, and growth in children.

2 Methods and results

We monitored 37 paediatric patients with sickle cell anaemia who were treated with hydroxyurea at a single UK treatment centre. Therapy was well tolerated and mild transient cytopenias were the only toxicity observed. Comparative analysis of patients receiving ≥26 mg/kg/day versus <26 mg/kg/day demonstrates increasing dose has a significant positive effect on foetal haemoglobin (Hb; 29.2% vs. 20.4%, P = 0.0151), mean cell volume (94.4 vs. 86.5, P = 0.0183) and reticulocyte count (99.66 × 10⁹/l vs. 164.3 × 10⁹/l, P = 0.0059). Marrow suppression was not a clinical problem with high‐dose treatment, Hb 92.25 g/l versus 91.81 g/l (ns), neutrophil count 3.3 × 10⁹/l versus 4.8 × 10⁹/l (ns) and platelet count 232.4 × 10⁹/l versus 302.2 × 10⁹/l (ns). Normal growth rates were maintained in all children. Good adherence to therapy was a significant factor in reducing hospitalisations.

3 Conclusion

This study demonstrates the effectiveness and safety in practice of high‐dose hydroxyurea as a disease‐modifying therapy, which we advocate for all children with sickle cell anaemia.