Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment.

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors.

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods: A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results: A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions: GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

Investigating racial disparities in quality-of-life years after pediatric hematopoietic stem cell transplant.

BACKGROUND: While racial disparities in the clinical outcomes of hematopoietic stem cell transplant (HSCT) patients have been explored, racial disparities in quality of life (QoL) during the re-adjustment phase after transplant are yet to be investigated in pediatric patients. The objective of this study was to examine the role of patient race in QoL at least 2 years after pediatric HSCT. PROCEDURE: We conducted a retrospective chart review of patients under 21 years of age at diagnosis who received an allogeneic transplant at our institution between January 2007 and December 2017. Patient QoL was assessed using the Pediatric Quality-of-Life Inventory Generic Score Scales (PedsQL TM 4.0) at least 2 years post transplant. Patient demographic, treatment, and transplant outcome data were obtained for subsequent analysis, where patient race was categorized as either Black, White, Hispanic, or Native American. RESULTS: Data were collected on 86 pediatric patients who underwent HSCT. Forty patients (46.5%) were non-Hispanic White, 29 (33.7%) Hispanic, 10 (11.6%) Black, and seven (8.1%) Native American. Where preliminary analyses indicated a difference in QoL by patient race, there were no significant differences in physical, emotional, social, and school functioning by patient race after adjusting for transplant characteristics (age at transplant, sex, diagnosis, donor type, and conditioning regimen) and determinants of socioeconomic status (insurance type, estimated household income). CONCLUSIONS: Pediatric patients had comparable QoL, regardless of race, at a median of 3 years after HSCT in our study cohort.

Efficacy of Azacitidine and Prophylactic Donor Lymphocyte Infusion after HSCT in Pediatric Patients with Acute Myelogenous Leukemia: A Retrospective Pre-Post Study.

Pediatric patients with acute myeloid leukemia (AML) who undergo allogeneic hematopoietic stem cell transplantation (HSCT) continue to have high rates of relapse. In 2018, Phoenix Children's Hospital started using post-HSCT maintenance therapy in patients with AML in attempt to decrease the number of relapses after HSCT. This therapy consisted of the hypomethylating agent azacitidine (AZA; 6 cycles starting on day +60) and prophylactic donor lymphocyte infusion (DLI; 3 escalating doses beginning after day +120). We aimed to compare 2-year leukemia-free survival (LFS) post-HSCT between patients with AML who received post-HSCT maintenance therapy with AZA and prophylactic DLI and historical control patients who did not receive post-HSCT therapy. This retrospective pre-post study was conducted at Phoenix Children's Hospital and included patients with AML who underwent HSCT between January 1, 2008, and May 31, 2022. We compared LFS, overall survival (OS), and immune reconstitution patterns post-HSCT between patients with AML who received post-HSCT maintenance therapy with AZA and prophylactic DLI (postintervention group) and historical control patients who did not receive this post-HSCT maintenance therapy (preintervention group). Sixty-three patients were evaluable. After excluding 7 patients who died or relapsed prior to day +60, 56 patients remained, including 39 in the preintervention group and 17 in the postintervention group. The median age at transplantation was 9.1 years in the preintervention group and 11 years in the postintervention group (P = .33). The 2-year LFS was 61.5% in the preintervention group, compared to 88.2% in the postintervention group (P = .06). The 2-year OS was 69.2% in the preintervention group and 88.2% in the postintervention group (P = .15). The rates of CD3+CD4+ T cell and CD19+ B cell recovery were faster in the preintervention group compared to the postintervention group (P = .004 and .0006, respectively). In this limited retrospective study, post-HSCT maintenance therapy using AZA and prophylactic DLI was well tolerated; however, its efficacy is yet to be fully determined.

Azacitidine and prophylactic donor lymphocyte infusions after hematopoietic stem cell transplantation for pediatric high-risk acute myeloid leukemia.

Post-hematopoietic stem cell transplantation (HSCT) maintenance therapy using azacitidine and prophylactic donor lymphocyte infusions (DLI) was implemented for high-risk acute myeloid leukemia. Azacitidine was started on day +60 as a 5 day course every 28 days for 6 cycles. DLI was given every 6 weeks for 3 doses starting after day +120. Ten patients were treated on this protocol. With a 90% one-year disease free survival, we report this post-HSCT maintenance therapy is feasible, safe, and well tolerated.

Adolescent male fertility following reduced-intensity conditioning regimen for hematopoietic stem cell transplantation in non-malignant disorders.

INTRODUCTION: The effects of RIC for HSCT on male fertility remain unknown. We investigated spermatogenesis and gonadal hormonal status among adolescent male patients who received RIC HSCT for non-malignant diseases. PATIENTS AND METHODS: Patients with non-malignant disease who had undergone a RIC HSCT were recruited and evaluated for spermatogenesis via semen analysis and gonadal hormonal function via serum hormone levels. Those who had received prior chemotherapy or radiation were excluded from the study. We reviewed the charts to record demographic factors, conditioning regimen and complications during and after transplant. RESULTS: Five patients were enrolled. The median age at the time of transplant was 15 years (range, 11-19 years), and the median time between bone marrow transplant and semen analysis was 5 years (range, 3-11 years). Median age of patients was 20 years (range, 18-25 years) at the time of the study. Serum FSH and LH levels were elevated in four patients, and inhibin B levels were low for age in three patients. Semen analysis showed two patients had azoospermia, and the remaining three patients showed severe oligozoospermia. Normal morphology and motility were seen in only one patient. CONCLUSION: This case series suggests that RIC transplants may be associated with impaired spermatogenesis and sequential follow-up is necessary given the potential for either permanent impairment or delayed recovery. Further larger studies are needed to confirm these findings.

Successful treatment of severe refractory autoimmune hemolytic anemia after hematopoietic stem cell transplant with abatacept.

BACKGROUND: After hematopoietic stem cell transplantation (HSCT) autoimmune hemolytic anemia (AIHA) is a known and fairly common complication. It is often refractory to conventional therapies including corticosteroids, intravenous immunoglobulin, splenectomy, and the more recently described use of monoclonal antibodies. The high morbidity associated with these severe persistent cases elucidates the gaps in alternative therapies available for treatment. STUDY DESIGN AND METHODS: We described the successful use of abatacept for severe refractory AIHA after HSCT in three patients. RESULTS: Three pediatric patients with refractory AIHA after allogeneic stem cell transplantation were observed to be unresponsive to multitude immunosuppressive therapies, resulting in persistent transfusion dependency. Treatment with abatacept, a fusion protein that inhibits T-cell activation by binding to CD80/CD86 on antigen-presenting cells (APCs), thus blocking the required CD28 interaction between APCs and T cells, resulted in the resolution of hemolysis. CONCLUSION: Abatacept may provide significant clinical benefit in the management of AIHA after HSCT.

Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant: Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression.

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by ΔN. The disease-free survival of this group was 10% (0 to 35%) compared with 55% (46% to 64%, P < .001) for those without disease. The ΔN assay was validated using the post-HSCT specimen by sorting abnormal or suspicious cells to confirm recipient or donor origin by chimerism studies. All 15 patients who had confirmation of tumor detection relapsed, whereas the 2 patients with suspicious phenotype cells lacking this confirmation did not. The phenotype of the relapse specimen was then used retrospectively to assess the pre-HSCT specimen, allowing identification of additional samples with low levels of MRD involvement that were previously undetected. Quantitative assessment of WT1 gene expression was not predictive of relapse or other outcomes in either pre- or post-transplant specimens. MRD detected by ΔN was highly specific, but did not identify most relapsing patients. The application of the assay was limited by poor quality among one-third of the specimens and lack of a diagnostic phenotype for comparison.

Antiviral T Cells for Adenovirus in the Pretransplant Period: A Bridge Therapy for Severe Combined Immunodeficiency.

Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections.

Evaluation of Revised International Staging System (R-ISS) for transplant-eligible multiple myeloma patients.

The International Myeloma Working Group has proposed the Revised International Staging System (R-ISS) for risk stratification of multiple myeloma (MM) patients. There are a limited number of studies that have validated this risk model in the autologous stem cell transplant (ASCT) setting. In this retrospective study, we evaluated the applicability and value for predicting survival of the R-ISS model in 134 MM patients treated with new agents and ASCT at the Mayo Clinic in Arizona and the University Hospital of Salamanca in Spain. The patients were reclassified at diagnosis according to the R-ISS: 44 patients (33%) had stage I, 75 (56%) had stage II, and 15 (11%) had stage III. After a median follow-up of 60 months, R-ISS assessed at diagnosis was an independent predictor for overall survival (OS) after ASCT, with median OS not reached, 111 and 37 months for R-ISS I, II and III, respectively (P < 0.001). We also found that patients belonging to R-ISS II and having high-risk chromosomal abnormalities (CA) had a significant shorter median OS than those with R-ISS II without CA: 70 vs. 111 months, respectively. Therefore, this study lends further support for the R-ISS as a reliable prognostic tool for estimating survival in transplant myeloma patients and suggests the importance of high-risk CA in the R-ISS II group.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2-Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues.

Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provide standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. We consider the available evidence using the GRADE criteria.

The Role of Thromboelastography in Pediatric Patients with Sinusoidal Obstructive Syndrome Receiving Defibrotide.

Sinusoidal obstructive syndrome (SOS) is a potentially fatal form of hepatic injury after hematopoietic stem cell transplantation. Patients can develop liver dysfunction, portal hypertension, ascites, coagulopathies, and multisystem organ failure. The mortality rate of severe SOS has been reported as high as 98% by day 100 after transplantation. Defibrotide, which is now approved for the treatment of SOS, has significantly decreased mortality. Defibrotide is a polynucleotide with profibrinolytic, anti-ischemic, and anti-inflammatory activity. These properties can increase the risk of life-threatening bleeding in this patient population. Previous protocols have suggested maintaining international normalized ratio ≤ 1.5, platelets > 30 k/uL, and fibrinogen ≥ 150 mg/dL to minimize this risk of bleeding. However, this can be challenging in fluid-sensitive patients with SOS. Thromboelastography (TEG) is a functional assay that evaluates the balance of procoagulant and anticoagulant proteins. In this series, TEG was used to guide defibrotide therapy as well as blood product transfusions in SOS patients with abnormal coagulation studies. Each patient recovered from SOS and had no bleeding complications. A randomized clinical trial is the next step in supporting the use of TEG in SOS patients with abnormal coagulation studies receiving defibrotide therapy.

Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis.

BACKGROUND: Graft-versus-host disease (GVHD) is the major limitation of allogeneic haemopoietic stem-cell transplantation (HSCT), for which no approved treatments are available. Use of mesenchymal stromal cells (MSCs) has become standard practice in some European countries, but controversy exists for their benefit. The aim of this meta-analysis was to analyse available evidence for the benefit of MSC treatments in steroid-resistant acute GVHD. METHODS: We did a systematic review and meta-analysis to assess response to and survival after MSC treatment in patients with steroid-refractory acute GVHD. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which MSCs were administered to patients with steroid-refractory acute GVHD. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was survival at 6 months from the first infusion of MSCs. FINDINGS: We identified 628 citations with our search, of which 610 were excluded after review and a further five did not contain pertinent data. Thus, our meta-analysis included 13 non-randomised studies at moderate risk of bias, comprising a total of 336 patients. Six studies provided data for the primary outcome analysis (119 patients). Survival at 6 months after MSC treatment was 63% (95% CI 50-74; I(2)=41%). Survival did not differ with respect to age, MSC culture medium, or dose of MSCs delivered. INTERPRETATION: Available evidence suggests that infusion of MSCs could be an acceptable treatment for patients with steroid-refractory acute GVHD. Randomised clinical trials are needed urgently to assess different treatment modalities for steroid-refractory acute GVHD. FUNDING: None.

Increased CTLA-4(+) T cells and an increased ratio of monocytes with loss of class II (CD14(+) HLA-DR(lo/neg)) found in aggressive pediatric sarcoma patients.

BACKGROUND: There is little information regarding the composition of peripheral blood immunity in sarcoma patients and even less in the context of pediatric sarcomas. We describe the immune status using flow cytometry of peripheral blood in patients with osteosarcoma and Ewing sarcoma and demonstrate excessive CD14 in tumor tissues. METHODS: Peripheral blood from patients with OS and ES was collected at diagnosis or relapse, and used for immune phenotyping of 74 different leukocyte phenotypes. Blood from young adult healthy volunteers was collected as controls. Tumor tissues were analyzed by immunohistochemistry. RESULTS: Nineteen patients (average age = 14 y) and 16 controls (average age = 25y) were enrolled on study. Of the 74 phenotypes, 14 were different between sarcoma patients and HV. Sarcoma patients' leukocytes contained a higher percentage of granulocytes (67 % sarcoma vs. 58 % HV; p = 0.003) and fewer lymphocytes (20 % sarcoma vs. 27 % HV; p = 0.001). Increased expression of CTLA-4 was seen in both T cells in sarcoma patients as compared to HV (p = 0.05). Increased CD14(+) HLA-DR(lo/neg) immunosuppressive monocytes were seen in sarcoma patients (p = 0.03); primarily seen in OS. Increased tumor necrosis factor receptor II expression was seen on CD14(+) cells derived from sarcoma patients as compared to HV (p = 0.01). Massive infiltration of CD14(+) cells was seen in OS (>50 % of cells in the majority of tumors) compared to ES (<10-25 % of cells). In contrast, both OS and ES had limited T cell infiltration (generally <10 % of cells). CONCLUSIONS: Pediatric sarcoma patients exhibit several immune phenotypic differences that were exacerbated in more severe disease. These phenotypes have the potential to contribute to immune suppression and may indicate potential targets for immune therapies.

Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch.

Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient- and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health-defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI.

Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase.

The prognosis for patients with Philadelphia-negative myeloproliferative neoplasms (MPN) who evolve into acute myeloid leukemia (AML) or blast phase (MPN-BP) is extremely poor. Although allogeneic stem cell transplantation (allo-SCT) is considered potentially curative, very few patients have been reported who have undergone allo-SCT for MPN-BP; therefore the success rate remains unknown. In a retrospective review, we identified 13 patients with an MPN transformation to blast phase after a median 9 years (range 5 months to 30 years); 8 (median age 55) continued to allo-SCT within 6 months. Induction chemotherapy cleared blood/marrow blasts in 60% (6/10) (2 declined therapy, 1 had early death). At the time of allo-SCT, 5/8 patients were in complete remission (CR) of their leukemia or had returned to MPN chronic phase (CP), 2 had residual blood blasts and 1 was refractory with >5% marrow blasts. At follow-up (median 20.3 months), 6 patients are alive in CR of both their leukemia/MPN. All 5 patients in CR/CP at pre-allo-SCT remain alive in remission, while 2/3 with persistent blood/marrow blasts relapsed and expired. We conclude that MPN-BP can be cured by allo-SCT in a significant percentage of patients, but that adequate leukemic clearance prior to allo-SCT offers an optimal outcome.

Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels.

Excessive adverse events were encountered in a Phase I/II study of cyclophosphamide (CY) dose deescalation in a fludarabine-based conditioning regimen for bone marrow transplantation from unrelated donors in patients with severe aplastic anemia. All patients received fixed doses of antithymocyte globulin, fludarabine, and low-dose total body irradiation. The starting CY dose was 150 mg/kg, with deescalation to 100 mg/kg, 50 mg/kg, or 0 mg/kg. CY dose level 0 mg/kg was closed due to graft failure in 3 of 3 patients. CY dose level 150 mg/kg was closed due to excessive organ toxicity (n = 6) or viral pneumonia (n = 1), resulting in the death of 7 of 14 patients. CY dose levels 50 and 100 mg/kg remain open. Thus, CY at doses of 150 mg/kg in combination with total body irradiation (2 Gy), fludarabine (120 mg/m(2)), and antithymocyte globulin was associated with excessive organ toxicity.

Coccidioidomycosis in hematopoietic stem cell transplant recipients.

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States that can cause devastating disseminated infection in immunocompromised persons. Clinical coccidioidomycosis, which is caused by Coccidioides species, has been well characterized in patients who have had solid organ transplants, but it has rarely been described in patients who have received a hematopoietic stem cell transplant (HSCT). We report the experience of 121 consecutive HSCT recipients at a single tertiary care institution in an endemic area. One patient had fatal disseminated coccidioidomycosis after receiving an allogeneic transplant, and 2 patients had pulmonary infection before successful autologous HSCT; 1 of these 2 had a reactivation of coccidioidal infection after HSCT but was treated and survived. Coccidioidomycosis was not commonly identified in HSCT recipients, even in the endemic area. A prospective evaluation is required to address the optimal use of coccidioidal serologic tests, antifungal protocols, and secondary prophylaxis in these patients.