The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as NCT02327351). Thirty-seven PID patients (median age, 2.6 years; range, .2 to 17) were transplanted from MUDs (n = 27) or haploidentical MMRDs (n = 10) after TCRαβ(+)/CD19(+) graft depletion. The median numbers of CD34(+) and TCRαβ(+) cells in the graft were 11.7 × 10(6)/kg and 10.6 × 10(3)/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUDs and MMRDs; 7 of these patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (nonengraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with 1 alkylating agent in the conditioning regimen. All these patients were successfully retransplanted with different rescue protocols. Preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/μL, on day +120. Based on our preliminary data, no significant difference was seen between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main post-transplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαβ(+)-depleted HSCT.
Immunocompromised patients, including HSCT recipients, may have a poor prognosis after contracting COVID-19 due to the absence of a pathogen-specific adaptive immune response. One of the possible options for severe COVID-19 treatment may be the transfusion of hyperimmune SARS-CoV-2 convalescent plasma.
A 9-month-old girl with juvenile myelomonocytic leukemia received an HSCT from a haploidentical donor. On day +99, during routine virologic monitoring, SARS-CoV-2 was detected without any clinical symptoms. On day +144, the child developed a polysegmental bilateral viral pneumonia with 60 % damage to the lung tissue and confirm a positive SARS-Cov-2 results in throat swab. The patient was treated with tocilizumab and three doses of fresh frozen plasma obtained from a SARS-CoV-2 convalescent patient.
Therapy with tocilizumab and three doses of fresh frozen plasma was well tolerated. In spite of full resolution of the lung lesions, complete elimination of SARS-CoV-2 has not been achieved 4 months after the first detection, which is due to persistence of secondary immunodeficiency after HSCT and the lack of reconstitution of the adaptive immune response.
This case represents a demonstration of an atypical course of COVID-19 and the delayed development of lung lesions, which was most likely associated with the features of the patient's immune status after HSCT. SARS-CoV-2 convalescent plasma in combination with other therapeutic approaches is one of the possible curative options for this clinical situation.
receiving bulk HPC infusion. In addition, CD4+ cell count on day 180, TRM and relapse rates were similar between the two groups. We also observed that with current mobilization techniques it was unlikely that more than 60% of normal donors would be able to collect more than 7x10E6 CD34+ cells/kg recipient weight for adult recipients.
The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. We present the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) with TCRab+/CD19+ graft depletion in patients with genetic hemophagocytic lymphohistiocytosis (HLH) at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology from 2012 to 2019. Thirty-six patients with various HLH: familial HLH (n = 20), X-linked lymphoproliferative disease (XLP) type 1 (n = 4), XLP type 2 (n = 9), Griscelli syndrome (n = 1), Chediak–Higashi syndrome (n = 2) received HSCT. Conditioning regimens were based on treosulfan in 9 patients, or on two alkylating agents: treosulfan with either melphalan, or thiotepa in 27 patients; all 36 patients received fludarabine and serotherapy. Thirty-two patients received rituximab 100 mg/m2 the day before stem cell infusion. Post- HSCT “graft versus host” disease (GvHD) prophylaxis was used in 29 patients. As a graft source peripheral blood stem cells from matched unrelated (n = 23), matched related (n = 3) and haploidentical family (n = 10) donors after TCRαβ+/CD19+ graft depletion were used. The cumulative incidence of primary and secondary graft failure in all patients was 0.11 (95% CI 0.04–0.29). The incidence of acute GvHD was limited to stage I-II. Overall survival was 0.91 (95% CI 0.82–1) without any significant differences in various donor groups (p = 0.33) as well as different conditioning regimens (p = 0.75). Allogeneic HSCT with TCRαβ+/CD19+ graft depletion after treosulfan-based conditioning is effective and safe technology for patients with genetic HLH.
Evans syndrome, a combination of autoimmune hemolytic anemia and immune thrombocytopenia, is a rare disease in children. In childhood, it may turn out to be one of the first manifestations of a primary immunodeficiency or an immune dysregulation syndrome. Here we present a clinical case of a patient who was initially diagnosed with Evans syndrome and did not respond well to therapy. Based on the results of genetic testing, the child was then diagnosed with primary immunodeficiency, namely, activated PI(3)kd syndrome. During follow-up, the patient developed lymphoma and had to undergo radical treatment (allogeneic hematopoietic stem cell transplantation). The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.
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