Allogeneic Hematopoietic Stem Cell Transplantation in Immunodeficiency-Centromeric Instability-Facial Dysmorphism (ICF) Syndrome: an EBMT/ESID Inborn Errors Working Party Study.

Immunodeficiency-Centromeric instability-Facial dysmorphism (ICF) syndrome is an inborn error of immunity characterized by progressive immune dysfunction and multi-organ disease usually treated with antimicrobial prophylaxis and immunoglobulin substitution. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment, but data on outcome are scarce. We provide a detailed description of disease characteristics and HSCT outcome in an international cohort of ICF syndrome patients. Eighteen patients (including all four genotypes) were enrolled. Main HSCT indications were infections (83%), enteropathy/failure to thrive (56%), immune dysregulation (22%) and myelodysplasia/haematological malignancy (17%). Two patients underwent pre-emptive HSCT after early diagnosis. Patients were transplanted between 2003-2021, at median age 4.3 years (range 0.5-19), after myeloablative or reduced-intensity conditioning, from matched sibling or matched family donors, matched unrelated or mismatched donors in 39%, 50% and 12% of cases respectively. Overall survival was 83% (all deaths occurred within the first 5 months post-HSCT; mean follow-up 54 months (range 1-185)). Acute GvHD occurred in 35% of patients, severe (grade III) in two (12%), while none developed chronic GvHD. At latest follow-up (median 2.2 years (range 0.1-14)), complete donor chimerism was achieved in 15/17 surviving patients. All survivors demonstrated normalized T and B cell numbers. Immunoglobulin substitution independence was achieved in all but two patients. All survivors recovered from pre-transplant infections, enteropathy/failure to thrive and immune dysregulation. All three patients transplanted at young age (≤ 3 years), after early diagnosis, survived. The favourable clinical and immunological HSCT outcome in this cohort of patients supports the timely use of this curative treatment in ICF syndrome.

Isolated Optic Nerve Relapse in a Pediatric Patient With T-Cell Lymphoblastic Leukemia: A Brief Report.

Isolated optic nerve (ON) relapse is a rare occurrence in lymphoblastic leukemia (LBL). A 10-year-old boy with T-LBL presented 8 months after diagnosis with blurred vision and thickening of right ON on magnetic resonance imaging consistent with relapse. Cerebrospinal fluid and bone marrow were negative for leukemia. He received reinduction chemotherapy (including nelarabine and craniospinal radiation) followed by a myeloablative matched sibling donor bone marrow transplant. He remains in remission 2 years post-transplant with normal vision. We also review the literature for reports of isolated ON relapse in patients with LBL. Our patient's clinical course demonstrates that disease control can be achieved with early detection of ON relapse before disease progression.

An International Survey of Allogeneic Hematopoietic Cell Transplantation for X-Linked Agammaglobulinemia.

PURPOSE: X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by variants in Bruton's tyrosine kinase (BTK). XLA patients require lifelong immunoglobulin replacement therapy (IgRT). Only few XLA patients are indicated for allogeneic hematopoietic cell transplantation (HCT) because of severe complications. Accordingly, the published transplantation experience in XLA is minimal. We aimed to collect clinical data of XLA patients who received HCT in an international framework and to establish appropriate transplantation criteria and methods for XLA patients. METHODS: XLA patients were recruited through a questionnaire and a literature review. The data are on patient characteristics and transplantation methods and outcomes. RESULTS: In this study, twenty-two XLA patients who underwent HCT were recruited. The indication for HCT was recurrent or life-threatening infection in sixteen patients, malignancy in three, and other factors in three. A myeloablative conditioning, reduced toxicity myeloablative conditioning (RT-MAC), and reduced intensity conditioning (RIC) were selected in four, ten, and eight patients, respectively. Engraftment was achieved in 21 patients (95%). In all patients, 2-year overall survival (OS) and event-free survival (EFS) were 86% and 77%, respectively. In patients who received RT-MAC or RIC using treosulfan, busulfan, or melphalan, 2-year OS and EFS were 82% and 71%, respectively. Finally, twenty-one patients (95%) obtained complete or stable high-level mixed chimerism (50-95%), and the 1-year discontinuation rate of IgRT was 89%. CONCLUSION: Based on the concept in which IgRT is the standard treatment for XLA, HCT may be an effective and safe alternative treatment option for XLA patients, and IgRT can be discontinued following transplantation. It is ideal to perform HCT in XLA patients for whom transplantation is indicated before they develop organ damage.

Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report.

Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. We report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers from 2005 through 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs ≥5 years of age at the time of HCT (94% vs 66%; overall P = .0008). OS was excellent regardless of donor type, even in cord blood recipients (90%). Conditioning intensity did not affect OS, but was associated with donor T-cell and myeloid engraftment after HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism <50% early after HCT. In addition, higher platelet counts were observed among recipients who achieved full (>95%) vs low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005, compared with prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution after either myeloablative or busulfan-containing reduced intensity conditioning. (This trial was registered at www.clinicaltrials.gov as #NCT02064933.).

Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers.

PURPOSE: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study's objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention. METHODS: We analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management. RESULTS: Infections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented. CONCLUSION: Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS. TRIAL REGISTRATION: NCT01186913.

A multicenter report on the safety and efficacy of plerixafor based stem cell mobilization in children with malignant disorders.

BACKGROUND: Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS: In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (<20 cells/cu.mm) (Group B1) or as a second collection process due to an unsuccessful yield (CD34 + < 2 × 106 /kg) (Group B2) following failed SM and first apheresis attempts. RESULTS: The study cohort (n = 47) with a median age of 8 (range 0.6-21) year, comprised 19 (40%) Group A and 28 (60%) Group B patients (B1 = 12 and B2 = 16). Pleraxifor mobilization was successful in 87.2% of patients, similar between Groups A and B (84.2% vs 89.2%) and resulted in a median 4-fold increase in PB CD34. Median number of apheresis attempts was 2 in Groups A and B1 but 4 in Group B2. In Group B2, median total CD34+ yield post-plerixafor was 9-fold higher than after SM (P = .0013). Mild to moderate transient adverse events affected 8.5% of patients. Among patients who proceeded to autologous transplant (n = 39), all but one engrafted. CONCLUSION: Plerixafor-based PBSC collection was safe and effective in our cohort and supports consideration as a primary mobilizing agent in children with malignancies.

Use of belatacept as alternative graft vs host disease prophylaxis in pediatric allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Immunosuppressive prophylaxis is usually given to decrease the development of acute graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Belatacept is a Cytotoxic T-lymphocyte-associated protein 4, blocking agent, an immunosuppressive agent used for organ rejection prevention in adult renal transplant recipients. METHODS: We describe two children in whom belatacept was successfully used for GvHD prophylaxis. Case 1 was noncompliant with prior immunosuppressive therapy for aplastic anemia, and Case 2 developed severe thrombotic microangiopathy (TMA) precluding the use of calcineurin inhibitors (CNI) or mTOR inhibitors. RESULTS AND CONCLUSION: Belatacept was found to be a safe alternative in preventing GvHD in 2 patients in whom traditional prophylactic therapies were not possible to use.

Costs of Cord Blood Transplantation Are Higher Than Other Graft Sources in Patients with Acute Leukemia and Myelodysplastic Syndrome Treated at Pediatric Centers.

In this commentary, we discuss the reasons why umbilical cord blood (UCB) allogeneic stem cell transplants are more expensive than matched related and matched unrelated peripheral blood and bone marrow transplants in patients treated at pediatric centers. We compare results of our previously published study with the recently published study from the Center for International Bone Marrow Transplant and Research/Pediatric Health Information System and also highlight the factors that contribute to increased costs of UCB transplants.

Refractory Thrombocytopenia Is a Valid Early Diagnostic Criteria for Hepatic Veno-Occlusive Disease in Children.

We compared the incidence of refractory thrombocytopenia (RT) and platelet transfusion requirements (PTR) in 35 children who developed veno-occlusive disease (VOD) with 35 matched control subjects who underwent hematopoietic stem cell transplant but did not develop VOD. RT developed in 100% of the VOD patients, at a median of 8 days before VOD diagnosis, as compared with 71.5% of the control group. VOD patients required more platelet transfusions than control subjects (median PTR, 6.9 mL/kg [range, .57 to 17.59] versus 3.57 mL/kg [range, 0 to 14.63], respectively) with a statistically significant difference (P < .0001). The number of days with platelet requirements was significantly higher for VOD patients as compared with control subjects (median 68% versus 39%, P =< .0001). The PTR peaked at ~12 mL/kg/day, 2 days before VOD diagnosis, whereas the PTR in the control population was 5 mL/kg/day. The positive predictive value of developing VOD was 88.9% (95% confidence interval, 66.5% to 97%) in patients who were given >7 mL/kg/day of platelets during the at-risk period of days +3 to +13 after transplant. For patients who received >8 mL/kg/day of platelets, the positive predictive value of developing VOD was 86.7% (95% confidence interval, 61.2% to 96.4%). There was no difference in the PTR in patients with mild to moderate VOD as compared with severe VOD; however, the PTR was higher in patients whose VOD did not resolve. The median daily PTR after the diagnosis of VOD in 17 patients who got defibrotide as compared with those who did not get defibrotide was 6.04 mL/kg and 5.72 mL/kg, respectively, but the difference was not statistically significant (P = .56). On univariate and multivariate analysis use of intravenous immunoglobulin was significantly associated with VOD (P = .0088) but was not significantly associated with fatal VOD. In conclusion, RT occurs in 100% of patients at a median of 8 days before VOD diagnosis. VOD should be suspected in any patient with RT after the exclusion of other causes of consumptive thrombocytopenia, especially if they require >7 mL/kg/day of platelets.

Increased Health Care Utilization and Costs during Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia and Myelodysplastic Syndromes in Adolescents and Young Adults Compared with Children: A Multicenter Study.

Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute leukemia and myelodysplastic syndromes (MDS) but is associated with significant cost. Compared with children (age <15 years), adolescents and young adults (AYA; age 15 to 39 years) undergoing HCT have an increased risk for transplantation-related complications. However, whether such complications translate into increased resource utilization and costs during HCT remains unknown. Therefore, we conducted a multicenter database study using the Pediatric Health Information System database, an administrative database containing resource utilization data from 49 US tertiary children's hospitals to compare inpatient costs and resource utilization in children and AYA undergoing HCT for acute leukemia and MDS. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients and transplantation-related complications occurring up to 1 year post-HCT. We identified 1693 HCT recipients at pediatric centers between January 2010 and September 2014. Eighty percent of the total costs (from admission for HCT up to 1 year post-HCT) occurred during the initial transplantation admission. During initial admission, although AYA and children had a similar median length of stay (LOS) of 43 days, AYA incurred significantly greater adjusted costs ($338,458 versus $275,723; P < .001) and costs per hospital day ($7122 versus $5838; P < .001). Median total costs and costs per day during subsequent time periods post-HCT were also significantly greater in the AYA group. In multivariable analysis, increasing age at HCT, LOS, use of cord blood or an unrelated donor, occurrence of any graft-versus-host disease, infection, and use of dialysis or mechanical ventilation were significant drivers of increased cost at initial admission. In conclusion, allogeneic HCT for acute leukemia and MDS is associated with higher costs in AYA recipients than in children. Therefore, directing efforts and resources aimed at reducing HCT-related costs may be advantageous in this high-risk group.

Successful treatment with eculizumab for posterior reversible encephalopathy syndrome due to underlying transplant-associated thrombotic microangiopathy in patients transplanted for sickle cell disease.

Preexisting endothelial dysfunction and vascular injury sustained during allogeneic hematopoietic cell transplantation (HCT) increases risk for endothelial injury-related complications such as posterior reversible encephalopathy syndrome (PRES) and transplant-associated thrombotic microangiopathy (TA-TMA) in patients with sickle cell disease (SCD). We report two patients with SCD who developed PRES following allogeneic HCT. In both patients, PRES-related symptoms resolved only after a diagnosis of TA-TMA was established and eculizumab therapy was initiated. Renal manifestations at diagnosis included non-nephrotic range proteinuria and hypertension. This report highlights the importance of screening PRES-affected SCD HCT recipients for TA-TMA as usual treatment strategies may be inadequate.

Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease.

Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.

Venous Thromboembolism in Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study.

Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus <13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.

70% Ethanol for Decontamination of Central Venous Lines Exposed to Calcineurin Inhibitors.

BACKGROUND: Tacrolimus, commonly used for graft versus host disease prophylaxis is usually administered via a dedicated central venous line (CVL) and trough levels drawn from the unexposed lumen. Being an oil-based medication, it may be adsorbed to the inner lumen of the CVL and result in falsely high levels drawn from an inadvertently exposed lumen. There is no treatment for decontamination of such CVLs, and natural decay occurs over months before the CVL can be used to draw reliable trough levels. OBJECTIVE: The primary objective of the study was to estimate the effectiveness of 70% ethanol locks for decontaminating CVLs exposed to tacrolimus. METHODS: We studied the efficacy of 70% ethanol lock in decontaminating CVLs exposed to tacrolimus in patients during transplant. Trough tacrolimus levels were drawn from the exposed and unexposed (control) lumens at 8:00 am, followed by a 2-mL 70% ethanol lock instilled for a 2-hour dwell into the exposed (intervention) lumen. Trough tacrolimus levels were again drawn from both lumens at 8:00 pm and levels compared for efficacy. RESULTS: All 20 sets showed a high 8 am trough level in the exposed intervention arm (median = 30 ng/mL), significantly greater ( P < 0.0001) than that in the control arm (median = 9.05 ng/mL), and were contaminated. After the 2-hour ethanol lock, 65% of the lumens were decontaminated. The difference between the control and intervention arms was no longer found to be statistically significant ( P = 0.0826). CONCLUSION: A 2-hour 70% ethanol lock is effective for decontamination of CVLs exposed to tacrolimus.

Post-hematopoietic stem cell transplant hemophagocytic lymphohistiocytosis or an impostor: Case report and review of literature.

HLH occurring after HSCT is a relatively rare disease. Many conditions may mimic or trigger HLH in post-HSCT period (eg, cytokine release syndrome, engraftment syndrome, graft rejection/failure, acute graft-vs-host disease, infections systemic inflammatory response syndrome/sepsis, and thrombotic microangiopathy). Moreover, this period is usually marked by febrile illness, cytopenia, and a "cytokine storm" leading to elevation of inflammatory biomarkers like ferritin and sCD25. These parameters overlap with the diagnostic criteria for HLH. Such confounding factors make the management of post-HSCT HLH quite challenging. We illustrate this critical issue with case report of a patient who was diagnosed with HLH after allogeneic HSCT for tAML. He received MP and CsA for HLH but VP-16 was not administered due to fear of severe myelosuppression. Fortunately, he responded well to treatment and remains in remission to date. We recommend caution while using HLH-94/HLH-2004 guidelines for the diagnosis and management of post-HSCT HLH. In this article, we pinpoint these issues with a brief review of all the pediatric cases and clinical studies of post-HSCT HLH along with a critical evaluation of its various diagnostic criteria. Finally, based on the limitations of current diagnostic criteria, we suggest a need for formulating disease-specific diagnostic criteria for post-HSCT HLH.

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia.

AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.

The role of continuous renal replacement therapy in the management of acute kidney injury associated with sinusoidal obstruction syndrome following hematopoietic cell transplantation.

Maintaining fluid balance, pre- and post-MA-HCT is essential and usually requires frequent administration of diuretics. Hepatic sinusoidal obstructive syndrome is potentially life-threatening, especially when associated with AKI and MOF. This study describes six patients who developed AKI-associated SOS and diuretic-resistant FO who subsequently underwent CRRT using standardized management guidelines for fluid balance post-HCT. Retrospective chart review was done for HCT patients between September 2011 and October 2013 at a tertiary care children's hospital. Thirty-four patients underwent MA-HCT in the study period. Six patients had SOS complicated by diuretic-resistant FO and underwent CRRT. Defibrotide was used in three patients. Median time on CRRT was 10.5 days. Sixty-six percent (N = 4 of 6) of patients had full resolution of SOS symptoms with a mortality rate of 34% (N = 2 of 6). Among patients who had full recovery of SOS symptoms, one patient developed AKI, end-stage renal diseases and underwent kidney transplantation 34-months post-HCT. Thus, of six included patients, two died and one developed ESRD with only 50% (N = 3 of 6) good outcome. Use of a standardized, evidence-based fluid balance protocol and early initiation of CRRT for HCT-related AKI/SOS was associated with good outcomes.

Severe transplant-associated thrombotic microangiopathy in patients with hemoglobinopathies.

Incidence and severity of transplant-associated thrombotic microangiopathy (TA-TMA) in patients with hemoglobinopathies receiving hematopoietic cell transplant is unknown. We report the outcomes for two patients with TA-TMA who received eculizumab. A 2.5-year-old male with sickle cell disease developed TA-TMA-associated pericardial tamponade, severe hypertension, and acute kidney injury 2 months after transplant. A 7-year-old female with ß-thalassemia major developed TA-TMA-related acute kidney injury, severe hypertension, and seizures at 6 months after transplant. Both patients progressed to chronic kidney disease (CKD). In patients with hemoglobinopathies, preexisting endothelial dysfunction may place them at a greater risk for TA-TMA and subsequent CKD.

Azacitidine as a bridge to allogeneic hematopoietic cell transplantation in a pediatric patient with Fanconi anemia and acute myeloid leukemia.

HCT is the definitive therapy for patients with FA and AML. Conventional cytotoxic agents cause potential DNA damage, and currently, there is no established regimen for these patients prior to HCT. A 13-year-old male with FA and refractory AML was given azacitidine, achieved morphologic remission and underwent HCT. At 95 days after HCT, he relapsed. Azacitidine along with DLI was used as first salvage therapy. Azacitidine was overall well tolerated with minimal side effects. In patients with AML and FA, azacitidine can be considered an alternative to conventional chemotherapy.