Incidence and natural history of pure red cell aplasia in major ABO‐mismatched haematopoietic cell transplantation

Major ABO mismatching is not considered a contraindication to allogeneic haematopoietic stem cell transplantation (HSCT). Modern reduced‐intensity conditioning and reduced‐toxicity regimens cause much less myeloablation than conventional myeloablative regimens, such as cyclophosphamide with busulfan or total body irradiation, which may affect the incidence of pure red cell aplasia (PRCA). We estimated the incidence and described the natural history of PRCA in patients with major ABO‐mismatched donor stem cells. Between 2007 and 2008, 161 (27% of all patients undergoing HSCT) underwent allogeneic HSCT with major ABO‐mismatched stem cells and 12 (7·5%) of these patients developed PRCA. Thirty and ninety day T‐cell and myeloid cell chimerism and neutrophil and platelet engraftment did not differ between patients who developed PRCA and those who did not. The only risk factor associated with PRCA was the use of a fludarabine/busulfan conditioning regimen. All patients with PRCA needed red cell transfusion for several months after HSCT resulting in significant iron overload. Pure red cell aplasia resolved spontaneously in the majority (seven patients) but only resolved after stopping tacrolimus in three patients. Hence, after major ABO‐mismatched HSCT, the incidence of PRCA was 7·5% and it resolved spontaneously or after withdrawal of immunosuppression in the majority of patients.     

Pure red-cell aplasia following major and bi-directional ABO-incompatible allogeneic stem-cell transplantation: recovery of donor-derived erythropoiesis after long-term treatment using different therapeutic strategies

Blood group incompatibility between donor and recipient of allogeneic stem cell transplants may be associated with post-transplant erythroid aplasia. A total of 548 patients (pts) received allogeneic transplant for malignant and non-malignant hematologic disorders. In a retrospective analysis, the prevalence and outcome of pure red-cell aplasia (PRCA) in 44 pts with major and bi-directional ABO-mismatch were investigated. Bone marrow grafts were major ABO incompatible in 30 pts; there was bi-directional mismatch in the remaining 14 pts. The median number of transplanted mononuclear cells (NC) was 4.74 × 10⁸/kg (range 0.1–26.4) including CD34+ cells, 3.02 × 10⁶/kg (range 0.9–21.7). Granulocyte engraftment >0.5 × 10e9/l occurred after a median of 21 days (7–32), and platelet exceeded >50 × 10e9/l after a median of 23.5 days (12–109). Acute and chronic graft vs host disease (GVHD) developed in 23 (52%) and 26 (59%) of the patients, respectively. Six (13%) patients transplanted with major and bi-directional ABO-incompatibility developed PRCA. The treatment of PRCA consisted of plasmapheresis (PEX), rapid cyclosporine (CsA) discontinuation, donor lymphocyte infusions (DLI), erythropoietin (EPO), azathioprine, and rituximab. The therapy resulted in erythroid recovery in five out of six patients after a median of 13 months (range 3–16). The median number of transfused red blood cells (RBCs) was 36 U (range 8–57). With a median follow-up of 37 months, the 5-year probability of overall survival (OS) for the PRCA group was 66%. Major ABO mismatch may lead to delayed donor erythroid engraftment. It results in long-term transfusion dependence and, therefore, the risk of iron overload. The therapy is long lasting, but usually effective in majority of patients.     

Donor lymphocyte infusions for refractory pure red cell aplasia relapsing after both autologous and nonmyeloablative allogeneic peripheral stem cell transplantation

Pure red cell aplasia (PRCA) is characterized by a selective marrow aplasia of the erythroid compartment. Immunosuppressive therapy achieves good results in about 25% of cases, but relapses are frequent. Autologous or allogeneic haematopoietic stem cell transplantation (HSCT) may be valuable in selected patients. Here, we report details of a 29-year-old woman treated successfully by donor lymphocyte infusions (DLIs) following allogeneic HSCT for acquired refractory relapsed PRCA. The nonmyeloablative conditioning regimen consisted of cyclophosphamide 60 mg/kg/day for 2 days and fludarabine 30 mg/m(2) daily for 4 days. Haematopoiesis was still completely 'recipient' 1 month after allo-HSCT, but progressed to full donor engraftment after three doses of 'escalating' DLI. The possible role of a graft-versus-autoimmunity effect induced by allogeneic HSCT followed by DLI infusions in the treatment of the disease is discussed.     

Impact of nonmyeloablative conditioning regimens on the occurrence of pure red cell aplasia after ABO-incompatible allogeneic haematopoietic stem cell transplantation

BACKGROUND AND OBJECTIVES: In the setting of major ABO-incompatible allogeneic haematopoietic stem cell transplantation (HSCT), pure red cell aplasia (PRCA) is linked to the persistence of host residual plasma cells secreting antidonor isohaemagglutinins (HA) after transplantation. There are conflicting results regarding the impact of the intensity of conditioning regimen on the occurrence of PRCA after major ABO-mismatched HSCT. MATERIAL AND METHODS: To address this question, we compared two cases occurring after nonmyeloablative (NMA) and myeloablative (MA) HSCT and reviewed previous cases reported in the NMA setting. RESULTS AND CONCLUSIONS: We observed a delayed disappearance of antidonor HAs in the NMA setting, associated to a more prolonged period of red blood cells transfusion dependence than in the MA setting. In our case as in several others, the disappearance of antidonor HAs and resolution of PRCA were observed after reinforcement of the graft-versus-host effect (i.e. immunosuppression removal or donor leukocytes infusion).     

Prolonged red cell aplasia after major ABO-incompatible allogeneic hematopoietic stem cell transplantation: removal of persisting isohemagglutinins with Ig-Therasorb immunoadsorption

Delayed donor red cell engraftment and prolonged red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible myeloablative and non-myeloablative hematopoietic stem cell transplantation (HSCT). There is an intense debate about the impact on outcome, severity of hemolysis, association with graft-versus-host disease and survival after blood group-incompatible stem cell transplantation. Therefore, therapeutic strategies should be considered to avoid these possible complications. We present five patients, who received allogeneic HSCT from human leukocyte antigen-identical donors for hematological malignancies, which were treated with Ig-Therasorb immunoadsorption (five treatments/week) to remove persisting incompatible isohemagglutinins. After a median of 17 treatments (range 9-25), all the patients became transfusion independent with the presentation of donor's blood group. No side effects occurred during treatment. Ig-Therasorb immunoadsorption seems to be a promising therapeutic method for rapid, efficient and safe elimination for persisting isohemagglutinins for patients with PRCA after allogeneic hematological stem cell transplantation.     

Linezolid‐induced pure red cell aplasia in a patient with Staphylococcus epidermidis infection after allogeneic stem cell transplantation

Linezolid (LZD) is the first oxazolidinone antibiotic that is effective against drug‐resistant gram‐positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy. However, LZD‐induced pure red cell aplasia (PRCA) is very rare. A 56‐year‐old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation from a human leukocyte antigen‐matched and ABO blood type‐matched unrelated male donor. He had bacteremia caused by Staphylococcus epidermidis after engraftment of neutrophils and red blood cells. We first administered vancomycin, but then changed to intravenous LZD because of kidney damage. Two weeks after LZD therapy, the patient's hemoglobin and reticulocyte levels were 6.8 g/dL and 0.3%, respectively. Bone marrow examination revealed red blood cell aplasia (myeloid/erythroid ratio was 402). The patient showed rapid recovery of normal erythropoiesis within 2 weeks of LZD cessation. It is important to be aware of the hematological effects associated with LZD in the setting of stem cell transplantation,particularly for those with pre‐existing myelosuppression, renal insufficiency, and those receiving concomitant drugs that produce bone marrow suppression. We advocate that a reticulocyte count be performed periodically for detecting bone marrow suppression, including PRCA, during LZD therapy.     

Resistant pure red cell aplasia after allogeneic stem cell transplantation with major ABO mismatch treated by escalating dose donor leukocyte infusion

We report a case of pure red cell aplasia (PRCA) following allogeneic stem cell transplantation (SCT) with major ABO mismatch which proved resistant to all standard treatment options such as change in immunosuppressive treatment, high-dose erythropoietin (EPO) or plasma exchange. We therefore proceeded to administer five cycles of Rituximab therapy, without success. Finally, escalating doses of donor-derived leukocyte infusion (DLI) resolved the PRCA of our patient 415 d after bone-marrow transplantation (BMT) and 140 d after the first infusion of donor leukocytes. A review of the literature shows the efficacy of various treatments; the role of DLI and other treatment options are discussed. Furthermore, the underlying pathophysiological mechanisms especially with regard to the role of NK cells in alloreactivity after allogeneic SCT are explained.     

The effect of donor leukocyte infusion on refractory pure red blood cell aplasia after allogeneic stem cell transplantation in a patient with myelodysplastic syndrome developing from kostmann syndrome

We describe the clinical course of a patient who experienced refractory pure red cell aplasia (PRCA) after undergoing HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for refractory anemia with an excess of blasts in transformation that had evolved from Kostmann syndrome. The treatment for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) developing from Kostmann syndrome has not been standardized. We treated this patient with allo-PBSCT using a regimen combining high-dose cytosine arabinoside with granulocyte colony-stimulating factor, in addition to total body irradiation and cyclophosphamide without preceding intensive chemotherapy. The donor was ABO incompatible. Myeloid and platelet recoveries were achieved rapidly. Erythroid engraftment was not evident, however, and the patient was given a diagnosis of PRCA. Regimen-related toxicity and graft-versus-host disease (GVHD) were limited. The PRCA did not respond to various therapies, including the discontinuation of immunosuppressants for the induction of chronic GVHD, human recombinant erythropoietin, immunosuppressive treatment with steroids, cyclosporin A, and human anti-CD20 antibody (rituximab). The patient received transfusions 48 times until the resolution of his anemia by donor leukocyte infusion (DLI) at 25 months after PBSCT. He is now clinically well (performance status, 100%) with normal blood cell counts at 5 years after SCT. An in vitro study demonstrated that serum from the recipient blocked the differentiation of erythroid cells in the bone marrow. The results indicate that the conditioning regimen we describe seems safe and effective for those who have MDS/AML and that DLI might be a valuable approach for refractory PRCA after ABO-incompatible SCT.     

Late onset of autoimmune hemolytic anemia and pure red cell aplasia after allogeneic hematopoietic stem cell transplantation using in vivo alemtuzumab

Hemolytic anemia and pure red cell aplasia (PRCA) after allogeneic hematopoietic stem cell transplantation (HSCT) have been reported to be mainly related to ABO-incompatibility between donor and recipient. Autoimmune hemolytic anemia (AIHA) without ABO-incompatibility has been also reported after allogeneic HSCT, especially with T-cell depletion. However, optimal management of AIHA or PRCA remains unclear. A 54-year-old male with myelodysplastic syndrome (MDS) underwent haploidentical human leukocyte antigen-mismatched HSCT using in vivo alemtuzumab and developed AIHA and PRCA simultaneously 15 months after transplantation, following the administration of cidofovir and probenecid for persistent cytomegalovirus (CMV) antigenemia and retinitis. AIHA was successfully treated with rituximab, and subsequently PRCA with cyclosporine without relapse of MDS or recurrence of CMV infection. The clinical course suggested that AIHA was mainly caused by humoral immune response, while PRCA was mainly caused by cell-mediated immune response in this patient, although these immune responses might be related to each other.     

Changes of isoagglutinin titres after ABO-incompatible allogeneic stem cell transplantation

We investigated the changes in isoagglutinin titres in 62 patients who underwent ABO-incompatible allogeneic stem cell transplantation. After major [and/or (+/-) minor] ABO-incompatible transplantation, recipient-derived isoagglutinins against donor-type red blood cells (RBCs) disappeared more rapidly in unrelated recipients (P = 0.006) and in patients with acute graft-versus-host disease (GVHD, P = 0.025) than in sibling recipients and in patients without acute GVHD respectively. Pure red cell aplasia (PRCA) developed in 10 out of 35 evaluable patients who underwent major (+/- minor) ABO-incompatible transplantation, and the post-transplant increase of isoagglutinin titres was a significant predictor for the occurrence of PRCA. In five out of 36 patients who underwent minor (and/or (+/-) major) ABO-incompatible transplantation, donor-derived isoagglutinins against recipient RBCs were detectable without clinically overt haemolysis. Isoagglutinin titres against ABO antigens absent both on recipient and donor RBCs decreased during the early post-transplant period then rose subsequently in 24 out of 29 patients at (median) d 59 post transplant. Our study showed that changes in isoagglutinin titres might have clinical implications in the occurrence of immunohaematological complications such as PRCA or immune-mediated haemolysis, and might reflect immunohaematological reconstitution after transplantation. Furthermore, our data regarding time to disappearance of recipient-derived isoagglutinins against donor-type RBCs after major ABO-incompatible transplantation suggest the presence of a graft-versus-plasma cell effect.     

Neurological complications after intrathecal liposomal cytarabine application in patients after allogeneic haematopoietic stem cell transplantation

Liposomal cytarabine has been proven to be useful for the prevention and intrathecal treatment of neoplastic meningitis. It has no demonstrable myelosuppressive effects and may therefore be an attractive alternative for prophylaxis and treatment of the central nervous system (CNS) relapse after allogeneic haematopoietic stem cell transplantation (HSCT). The use of liposomal cytarabine had not been reported in HSCT recipients. We retrospectively reviewed the feasibility of liposomal cytarabine in the prophylaxis (n = 2) and treatment (n = 4) of neoplastic meningitis in a cohort of patients after allogeneic HSCT. This report focusses on neurological complications after intrathecal application of liposomal cytarabine. Mild headache was the most commonly reported adverse event. Two patients experienced sacral radiculopathy with irreversible cauda equina syndrome in one patient. Another patient progressed with pre-existing leukencephalopathy. Intrathecal liposomal cytarabine should be used very cautiously in allogeneic HSCT recipients with a history of CNS complications potentially involving cerebral-spinal fluid circulation, since significant neurotoxicity was observed in patients with extensive CNS-directed pre-treatment. The feasibility and safety of liposomal cytarabine in HSCT recipients has to be evaluated in a prospective study.     

High CD4/CD8 ratio in allografts predicts adverse outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation for chronic myeloid leukemia

HLA-mismatched/haploidentical hematopoietic stem cell transplantation (haplo-mismatched HSCT) has improved the outcome of chronic myeloid leukemia (CML) in patients without an HLA-matched donor. To further improve the treatment outcome of haplo-mismatched HSCT in CML, a modifiable prognostic factor needs to be found. The cellular composition of grafts obtained from 75 HLA-mismatched/haploidentical related donors was prospectively correlated with the outcome of patients with CML undergoing haplo-mismatched HSCT following a modified regimen of BU/CY 2 plus antithymocyte globulin. The concentration of T-cell subsets, CD14+, and CD34+ cells and their relative proportions were analyzed. In univariate analyses, disease-free survival (DFS) and overall survival (OS) conversely correlated with the CD4/CD8 ratio in primed bone marrow graft (G-BM) (p = 0.012 and p = 0.040); similarly, CD4/CD8 ratio in total grafts was also negatively associated with DFS and OS (p = 0.018 and p = 0.020). In multivariate analyses, a CD4/CD8 ratio in G-BM higher than the median value remained the only factor negatively affecting DFS (p = 0.030; 95% confidence interval [CI], 1.166–19.341). Expectedly, high CD34+ cell dose was associated with accelerated platelet engraftment (p = 0.009; 95% CI = 1.181–3.271) after controlling for a high risk of disease. No other clinical parameter was influenced by graft composition. Our results suggest that a high CD4/CD8 ratio in allografts may predict adverse survival in patients with CML undergoing haplo-mismatched HSCT. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Haematopoetic stem cell transplantation for refractory autoimmune cytopenia

This study describes the outcome of patients receiving haematopoietic stem cell transplantation (HSCT) to treat severe refractory autoimmune cytopenia. The registry of the European Group of Blood and Marrow Transplantation holds data on 36 patients receiving 38 transplants, the first transplant was autologous for 27 and allogeneic for nine patients. Patients had autoimmune haemolytic anaemia (autologous: 5; allogeneic: 2), Evans's syndrome (autologous: 2; allogeneic: 5); immune thrombocytopenia (autologous: 12), pure red cell aplasia (autologous: 4; allogeneic: 1), pure white cell aplasia (autologous: 1; allogeneic 1), or thrombotic thrombocytopenic purpura (autologous: 3). Patients had longstanding disease having failed multiple prior treatments. Among 26 evaluable patients mobilized for autologous HSCT, three died of treatment-related causes, one died of disease progression, seven were non-responders, six patients had transient responses and nine had continuous partial or complete remission. Of the seven evaluable patients receiving allogeneic HSCT, one died of treatment-related complications, one with transient response died of progressive disease and five had a continuous response. Autologous and allogeneic HSCT may induce a response in a subset of patients with autoimmune cytopenia of long duration albeit at the price of considerable toxicity.     

Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

Background

Persistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia.

Design and Methods

We investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipients with major ABO incompatibility.

Results

Twelve patients (8%) developed pure red cell aplasia, 3/98 (3%) with, and 9/55 (16%) without prior isoagglutinin reduction (p=0.009). Red blood cell engraftment was faster in patients with isoagglutinin reduction; in addition, peripheral blood hematopoietic stem cell transplantation, acute graft-versus-host disease, and younger age were associated with faster red blood cell engraftment in Cox regression analysis. In patients with pure red cell aplasia the mean red blood cell engraftment occurred after 225 days (p<0.001) and was associated with a simultaneous decrease of anti-donor isoagglutinins. Patients with pure red cell aplasia had higher pretransplant anti-donor isoagglutinin titers (p=0.001) and received more post-transplant red blood cell transfusions (p<0.001).

Conclusions

Following major ABO incompatible hematopoietic stem cell transplantation, pure red cell aplasia and delayed red blood cell engraftment depend on the levels of anti-donor isoagglutinins and are efficiently prevented by the pretransplant removal of these isoagglutinins. The benefits of reducing the time of transfusion-dependency and transfusion-associated risks must be carefully balanced against the potential side effects of isoagglutinin reduction.     

异基因造血干细胞移植治疗白血病76例临床观察

目的观察不同来源的异基因造血干细胞移植治疗白血病的疗效并探讨主要并发症的处理方案。方法对2001年9月至2007年3月第四军医大学西京医院血液科76例白血病患者行异基因造血干细胞移植治疗,其中慢性粒细胞白血病34例,急性髓性白血病24例,急性淋巴细胞白血病15例,T细胞淋巴瘤/白血病3例。人类白细胞抗原(HLA)全相合的同胞供者57例,1个HLA位点不合同胞供者3例,HLA单倍型半相合同胞供者7例,非血缘供者9例。预处理方案采用改良的马利兰联合环磷酰胺(BUCY)或改良的环磷酰胺联合全身放疗及阿糖胞苷或鬼臼乙叉甙(CyTBI Ara-c/VP-16)方案。采用标准的环孢素A(CsA)联合短期甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD);无关供者移植加用抗人胸腺细胞球蛋白,单倍型半相合移植同时加用CD25单克隆抗体。结果96.1%(73/76)获得植入。24.7%(18/73)出现急性GVHD,32.9%(24/73)出现慢性GVHD;合并重症肝静脉闭塞病2例;并发纯红细胞性再生障碍性贫血5例。随访3~72个月,现存活56.6%(43/76),43.4%(33/76)在移植后1~36个月时死亡,19例死于白血病复发,14例死于移植相关并发症。结论多种来源的异基因造血干细胞移植是治疗白血病的有效方法,于慢性粒细胞白血病慢性期、急性白血病缓解期移植效果较好,移植前处于高危难治状态的病例复发率仍较高。     

Clinical features and risk factors of pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation

The objective of this paper was to study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005. Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n = 9) or blood group B donor (n = 2). The following factors were associated with an increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and (3) blood group O/A in recipient/donor pair. Only blood group a/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Six patients who received donor-type plasma exchange did not develop PRCA and among them 5 cases were the blood group O recipients. Eight patients obtained spontaneous remission and in the remaining 3 patients 2 with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange and anti-CD20 monoclonal antibody is an effective approach for the treatment of PRCA. PRCA could be prevented by plasma exchange prior to transplantation.     

High-dose therapy with peripheral blood stem cell transplantation for patients with relapsed or refractory Hodgkin's disease: long-term outcome and prognostic factors

 From March 1986 to March 1998, 82 patients with relapsed or refractory Hodgkin's disease underwent high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) transplantation in our center. This is a retrospective analysis of the long-term clinical outcome. There were 52 males and 30 females with a median age of 32 years (range 18–59 years). Prior to transplantation, 36 patients were in complete remission (CR), 34 in partial remission (PR), and 12 had refractory disease after salvage therapy. For HDCT, 78 patients were treated with CBV (cyclophosphamide, 6.0–6.8 g/m²; etoposide, 1.0–1.6 g/m²; carmustine, 0.45–0.8 g/m²), while four patients received different regimens. Probability of freedom from progression (FFP), overall survival (OS), and event-free survival (EFS) at 5 years of the entire group was 63%, 61%, and 54%, respectively. Early mortality rate (≤100 days) declined from 17% to 6% after 1992. Five patients died of late transplant-related complications (>100 days), including secondary lymphoma and leukemia in two patients. None of the refractory patients survived beyond 3.5 years. Multivariate analyses identified extranodal sites of disease at relapse and refractory disease status prior to transplantation as significant prognostic factors for FFP, EFS, and OS. As we have shown in our study, remarkable progress was achieved in reducing early morbidity and mortality over time, but this was associated with only a slight, not significant improvement of long-term outcome (OS 66% vs 57% at 5 years for patients undergoing PBSC transplantation before and after 1992, P=0.26). Although the results as a whole are encouraging for chemosensitive patients, new therapeutic strategies are needed to reduce toxicity and improve the clinical outcome of patients, especially of those with a less favorable prognosis. Received: 12 October 1999 / Accepted: 29 February 2000     

Successful treatment of refractory red cell aplasia after allogeneic hematopoietic cell transplantation with daratumumab

Pure red cell aplasia (PRCA) is an uncommon complication secondary to ABO mismatched allogeneic stem-cell transplantation (allo-HSCT). The best approach for PRCA after allo-HSCT remains unclear. We aim to report a single case with refractory PRCA post-ABO mismatched allo-HSCT resolved with daratumumab. A 34-year-old male diagnosed with aplastic anemia in March 2014 received a peripheral blood reduced-intensity allo-HSCT from an HLA-matched related donor in July 2016. Donor and recipient blood groups were AB positive and 0 positive, respectively, indicating a major ABO incompatibility. The patient was diagnosed with PRCA 2 months after allo-HSCT. After failing multiple standard lines of treatment, compassionate treatment with daratumumab was requested. After receiving six doses of daratumumab, the patient had a marked reticulocyte response and consecutively become transfusion independent. In conclusion, Daratumumab is a human IgG1κ monoclonal antibody targeting CD38 and is used to treat multiple myeloma. The use of anti-CD38 therapy with daratumumab to target residual host plasma cells is safe and effective, and it can be considered in refractory recipients with PRCA after allo-HSCT secondary to ABO incompatibility.     

Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis

Graft-versus-host disease (GVHD) is a major cause of transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T-cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose-finding study, 19 adults (median age: 54 years) with high-risk haematological malignancies were treated with T-cell-depleted human leucocyte antigen-haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 × 10⁴–5 × 10⁶ CD3⁺ cells/kg (median 31 days post-transplant). No patient received post-transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long-term follow -up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0·3–2 × 10⁶ CD3⁺ cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0%, relapse-related mortality was 33% and overall survival was 67% in these patients.     

Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation

Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible hematopoietic stem cell transplantation (SCT) performed by means of myeloablative conditioning. To evaluate these events following reduced-intensity nonmyeloablative SCT (NST), consecutive series of patients with major ABO incompatibility undergoing either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Donor red blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood) was markedly delayed following NST versus myeloablative SCT (median, 114 versus 40 days; P <.0001) and strongly correlated with decreasing host antidonor isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically insignificant levels more slowly following NST than myeloablative SCT (median, 83 versus 44 days; P =.03). Donor RBC chimerism was delayed more than 100 days in 9 of 14 (64%) and PRCA occurred in 4 of 14 (29%) patients following NST, while neither event occurred in 12 patients following myeloablative SCT. Conversion to full donor myeloid chimerism following NST occurred significantly sooner in cases with, compared with cases without, PRCA (30 versus 98 days; P =.008). Cyclosporine withdrawal appeared to induce graft-mediated immune effects against recipient isohemagglutinin-producing cells, resulting in decreased antidonor isohemagglutinin levels and resolution of PRCA following NST. These data indicate that significantly delayed donor erythropoiesis is (1) common following major ABO-incompatible NST and (2) associated with prolonged persistence of host antidonor isohemagglutinins. The clinical manifestations of these events are affected by the degree and duration of residual host hematopoiesis.