Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient post-HSCT to reduce the adverse effects of GVHD. We monitored the numbers and phenotype of granulocytes. In this case study, an 11-year-old female patient, diagnosed with β-thalassemia major (Pesaro class II), was treated with Cy before and after HSCT with mobilized CD34+ cells. Both the relative and absolute granulocyte counts, as well as CD33+CD11b+ cell counts, increased significantly after HSCT until day 56. However, they suddenly began to decrease after day 56, accompanied by severe diarrhea, skin rash, and a decrease in bilirubin levels compared to day -12. Furthermore, compared to day -12, IL-22 levels increased until day 56, and then decreased, while IDO levels continued to rise after day 56. Our data suggest the potential use of IL-22 and IDO as biomarkers for GVHD assessment. It also indicates that Cy promotes HSCT reconstitution by increasing CD33+CD11b+ cells, which may play a crucial role in reducing GVHD risks. However, further studies are needed to elucidate the mechanism behind GVHD recurrence.

UNASSIGNED: Encephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication.
UNASSIGNED: Herein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered.
UNASSIGNED: We should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient\'s complete remission has persisted for 20 months after HSCT.

OBJECTIVE: Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence.
METHODS: We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests.
RESULTS: Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001).
CONCLUSIONS: We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a highly aggressive subtype of T-ALL. No standard chemotherapy regimen exists for patients with recurrent/refractory (R/R) ETP-ALL; in these patients, the primary goal of salvage therapy is to achieve remission as a foundation for consolidation and intensification treatments. This study reports cases of two patients with R/R ETP-ALL who underwent salvage therapy of venetoclax combined with the CAG regimen and achieved complete remission in the bone marrow. Flow cytometry results were negative for minimal residual disease. Both patients were bridged to allogeneic hematopoietic stem cell transplantation (HSCT) and in complete remission over a 3-year follow-up period. These cases show that the use of venetoclax combined with the CAG regimen may offer patients with R/R ETP-ALL an opportunity for allogeneic HSCT.

Here we describe the case of a 51 years old Italian woman with acute lymphoblastic leukemia who underwent to hematopoietic stem cell transplantation (HSCT) during SARS-COV-2 infection. She presented a prolonged COVID-19 successfully treated with dual anti SARS-COV-2 antiviral plus monoclonal antibody therapy.

Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Management of refractory CMV infections, especially in developing countries, can be challenging due to the limited availability of second and third-line antiviral drugs or alternative treatments. Here, we present a case of an 8 years-old patient diagnosed with acute myeloid leukemia. Eight months post-diagnosis, the patient underwent TCR-αβ+/CD19+-depleted haploidentical HSCT. Both the donor and recipient tested positive for anti-CMV IgG and negative for IgM antibodies. Before transplantation, the patient received CMV prophylaxis in the form of intravenous ganciclovir. Post-transplantation, the patient exhibited oscillating CMV viral loads and was diagnosed with a refractory infection. Treatment with ganciclovir, foscarnet, and cidofovir was unsuccessful. Sequencing of UL-54 and UL-97 genes was performed to rule out potential resistance to first-line treatment. Ten months after the HSCT, the child died from hypovolemic shock due to gastrointestinal bleeding. This is the first case reported in Peru and Latin America of a refractory CMV infection in a pediatric HSCT recipient without evidence of clinical symptoms and CMV genetic resistance. This case demonstrates the need for alternative treatments to manage refractory CMV infections, especially in haploidentical HSCT cases where drug resistance is frequent (~15%). Furthermore, this case highlights the importance of using highly sensitive genetic tools to detect mutations associated with virus resistance in a broader range of the viral genome.

UNASSIGNED: We report a case of an adult hematopoietic stem cell donor who developed active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the donation of stem cells, the final transplantation was successfully completed without SARS-CoV-2 transmission.
UNASSIGNED: We report on a 34-year-old female diagnosed with acute lymphoblastic leukemia who underwent hemiploid hematopoietic stem cell transplantation (HSCT). Both patient and donor received three doses of inactivated SARS-CoV-2 vaccine before transplantation. PB-HSC was collected by the donor during the process of infection with SARS-CoV-2 (mild), and the patient did not show symptoms related to SARS-CoV-2 after transplantation. Nucleic acid and antigen were negative in regular tests.
UNASSIGNED: In the context of the current Omicron epidemic and high vaccination rate in the population, it is feasible to receive PB-HSC from infected donors even for immunocompromised patients. This also provides some references for our later donor selection.

Cytomegalovirus (CMV) infection is one of the most common infectious complications following hematopoietic stem cell transplantation (HSCT); however, cases involving multiple organs at the same time are rare. The present study describes a case of CMV pneumonia combined with CMV DNAemia and CMV cystitis after HSCT. A 33-year-old male patient with acute myeloid leukemia was treated with HSCT. The first month after HSCT, the patient developed a cough and shortness of breath. At 2 months post-HSCT, the patient developed hematuria. The CMV DNA levels in the blood and urine were elevated; bronchoalveolar lavage fluid (BALF) was also positive for CMV DNA. Heterotypic cells exhibiting a large nuclear morphology were observed in the BALF and bronchial brushes. Recurrent and progressive ground-glass opacities were evident on chest computed tomography. The patient was diagnosed with CMV pneumonia complicated by CMV DNAemia and CMV cystitis, and was treated with a combination of ganciclovir and foscarnet, along with immunoglobulin therapy. The patient was cured and discharged. It was determined that the CMV DNA in the blood was inconsistent with that in the BALF, which delayed the early diagnosis of CMV pneumonia. The association between T-cell immune function and the therapeutic efficacy for CMV multi-organ infection following HSCT is known to be significant. Moreover, the timely administration of ganciclovir and foscarnet in combination with immunoglobulin therapy demonstrated favorable clinical outcomes.

BACKGROUND: Hemophagocytic lymphohistiocytosis is a life-threatening disease heralded by fever, cytopenia, hepatosplenomegaly, and multisystem organ failure. Its association with genetic mutations, infections, autoimmune disorders, and malignancies is widely reported.
METHODS: A 3-year-old male Arab Saudi patient with insignificant past medical history and parental consanguinity presented with abdominal distension of moderate severity and persistent fever despite receiving antibiotics. This was accompanied by hepatosplenomegaly and silvery hair. The clinical and biochemical profiles were suggestive of Chédiak-Higashi syndrome with hemophagocytic lymphohistiocytosis. The patient received the hemophagocytic lymphohistiocytosis-2004 chemotherapy protocol and had multiple hospital admissions mainly due to infections and febrile neutropenia. After achieving the initial remission, the patient\'s disease reactivated and did not respond to reinduction with the hemophagocytic lymphohistiocytosis-2004 protocol. Due to the disease reactivation and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent an uneventful hematopoietic stem cell transplantation.
CONCLUSIONS: Novel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, while avoiding the toxicities of conventional therapy. Due to a paucity of available data on emapalumab, additional data are needed to establish its role in hemophagocytic lymphohistiocytosis treatment.