A Case Report of Lung Transplantation After Hematopoietic Stem Cell Transplantation and Literature Review

Pulmonary complications may occur after hematopoietic stem cell transplantation for hematologic malignancies. Lung transplantation is the only treatment option for end-stage lung failure. We presented a case of acute myeloid leukemia who received a hematopoietic stem cell transplantation and underwent bilateral lung transplantation with end-stage usual interstitial pneumonia and chronic obstructive lung disease. This case showed that lung transplantation could be successfully applied in properly selected hematologic malignancy patients with long disease-free survival, like lung transplantations performed for other indications.     

Skeletal Changes After Hematopoietic Stem Cell Transplantation in Osteopetrosis

Osteopetrosis is a rare skeletal dysplasia resulting from an osteoclast defect leading to increased bone mass and density. Hematopoietic stem cell transplantation can rescue the disease phenotype and prevent complications. However, little is known about the skeletal changes hematopoietic stem cell transplantation induces in patients with this disease. The purpose of this study was to describe the skeletal changes after hematopoietic stem cell transplantation in a retrospective cohort of patients diagnosed with osteopetrosis in one medical center over 13 years. For this purpose, all available epidemiological, hematological, biochemical, and radiographic data were collected and quantitatively analyzed. We found a significant early change in bone metabolism markers coinciding with hematopoietic recovery after stem cell transplantation. Hematopoietic stem cell transplantation induced a later significant improvement in both skeletal mineral distribution and morphology but did not lead to complete radiological normalization. Presumably, changes in bone metabolism, skeletal mineral distribution, and morphology were the result of renewed osteoclast function enabling bone remodeling. We propose that biochemical bone metabolism markers and radiological indices be routinely used to evaluate response to hematopoietic stem cell transplantation in patients with osteopetrosis. © 2020 American Society for Bone and Mineral Research.     

Successful Treatment of Veno-occlusive Disease,Transplantation-Associated Thrombotic Microangiopathy,and Acute Graft-vs-Host Disease in a Patient with Relapsed Epstein-Barr Hemophagocytic Lymphohistiocytosis After Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report

BackgroundAllogenic hematopoietic stem cell transplantation may be the best currently available method to treat relapsed hemophagocytic lymphohistiocytosis (HLH) related to Epstein-Barr virus. The high rate of transplantation-related complications was initially the main obstacle preventing the wider adoption of this protocol; however, the previously more common complications, such as infection and graft failure, have fallen to very low levels with the development of new drugs and methods. Some other complications, such as veno-occlusive disease and transplantation associated thrombotic microangiopathy, are rare after allogenic hematopoietic stem cell transplantation, but the morbidity and mortality associated with them are very high.Case presentationA patient with relapsed HLH related to Epstein-Barr virus showed the sequential severe complications of veno-occlusive disease, transplantation-associated thrombotic microangiopathy, and acute graft-vs-host disease after haploidentical transplantation. This patient was successfully treated by stopping administration of calcineurin inhibitors and instead treating with defibrotide, rituximab, CD25 monoclonal antibody, atorvastatin calcium tablets, methylprednisolone, budesonide, continuous plasma exchange, and bedside ultrafiltration. At the last follow-up, the patient had been living disease free for 2 years without any other complications.ConclusionEpstein-Barr virus related-HLH patients have severe clinical features and currently poor prognosis. Allogenic hematopoietic stem cell transplantation may be the best way to treat this disease; however, the management of related complications is vital in the improvement of long-term survival.     

造血干细胞移植

20世纪50年代初期造血干细胞移植兴起,随着医学科技发展,大剂量化疗（预处理）＋造血干细胞移植为各种晚期肿瘤和癌症治疗提供了有力的支持,目前对造血干细胞的来源、种类、采集、活性测定,异基因造血干细胞的配型、动员剂的效果、骨髓中癌细胞污染的处理、移植后并发症的诊治、疾病观察指标、临床适应证和治疗效果的评估等等都逐渐规范化,且有很多治疗成功病例的报告。     

Chronic kidney disease after hematopoietic stem cell transplantation

Acute and chronic kidney diseases occur after hematopoietic stem cell transplantation. These are caused by the transplant itself, and the complications of transplant. Recent estimates show that near 15% of subjects undergoing hematopoietic stem cell transplantation will develop chronic kidney disease, which is a complication rate that can affect outcome and reduce survival. Investigation of the causes of chronic kidney disease is needed, as are ways to prevent, mitigate, and treat it.     

Complications rénales au décours de la greffe de cellules souches hématopoïétiques

Hematopoietic stem cell transplantation is a widely used therapeutic modality for many, mainly malignant, diseases. Toxicities of this procedure include acute and chronic renal dysfunction. Acute renal failure, generally reversible is due to acute tubular necrosis (tumor lysis syndrome, marrow-infusion toxicity, sepsis, nephrotoxins), hepatic veno-occlusive disease or acute graft-versus-host disease. Chronic renal failure is often multifactorial, caused by conditioning-associated endothelial cell toxicity (bone marrow transplant nephropathy) and calcineurin inhibitors toxicity. Renal pathologic findings are somewhat similar to thrombotic microangiopathy, with sometimes systemic disease. Rare cases of nephrotic syndrome have been described after hematopoietic stem cell transplantation, mainly membranous nephropathy, associated with graft-versus-host disease. Therapeutic options for renal dysfunction after hematopoietic stem cell transplantation are limited but kidney transplantation is possible in case of end-stage renal disease.     

Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation

BACKGROUND: Hematopoietic cell transplantation may offer the only cure for patients with hematological diseases. The clinical application of this therapy has been limited by toxic conditioning and lack of matched donors. Haploidentical transplantation would serve to extend the potential donor pool; however, transplantation across major histocompatibility complex barriers is often associated with severe graft-versus-host disease. Here we evaluate a novel protocol to achieve engraftment across mismatch barriers without toxic conditioning or significant posttransplant complications. METHODS: Nine major histocompatibility complex (MHC)-defined miniature swine received haploidentical hematopoietic cell transplantation following standard myeloablative conditioning. Nine additional animals received haploidentical hematopoietic cell transplantation following a minimally myelosuppressive regimen, consisting of 100 cGy total body irradiation, immunotoxin mediated T-cell depletion, and a short course of cyclosporine. Donor cell engraftment and peripheral chimerism was assessed by polymerase chain reaction and flow cytometry. Graft-versus-host disease was monitored by clinical grading and histology of skin biopsy specimens. RESULTS: All animals conditioned for haploidentical hematopoietic cell transplantation using myeloablative conditioning were euthanized within 2 weeks due to engraftment failure or graft-versus-host disease. All animals conditioned with the nonmyeloablative regimen developed multilineage peripheral blood chimerism during the first 2 months following transplantation. Six animals evaluated beyond 100 days maintained multilineage chimerism in the peripheral blood and lymphoid tissues, showed evidence of progenitor cell engraftment in the bone marrow, and had minimal treatment-related complications. CONCLUSIONS: Here we report that stable multilineage chimerism and engraftment can be established across haploidentical major histocompatibility complex barriers with minimal treatment-related toxicity and without significant risk of graft-versus-host disease.     

Treatment of a Pediatric Case of Severe Hemorrhagic Cystitis: Case Report and Review of Literature

Hemorrhagic cystitis is one of the complications of allogeneic hematopoietic stem cell transplantation. Treatment of hemorrhagic cystitis is difficult, especially in pediatric patients. A pediatric case of severe hemorrhagic cystitis after hematopoietic stem cell transplantation was treated in our hospital with arterial embolization combined with corticosteroid therapy because the conventional therapy was invalid for him. After the treatment, hemorrhagic cystitis was cured. During follow-up, the patient was in stable condition, with normal urine, blood cells returned to normal, bone marrow was in complete remission state, and disease-free survival for more than 8 months. Selective bladder arterial embolism followed by corticosteroid therapy successfully treated the patient.     

Carcinoma of donor origin after allogeneic peripheral blood stem cell transplantation

Secondary cancers developing after allogeneic hematopoietic stem cell transplantation generally originate from recipient-derived cells. In this study, we analyzed the tumor cell origin of 5 epithelial malignant tumors (esophageal squamous cell carcinoma, lung adenocarcinoma, gastric adenocarcinoma, pharyngeal squamous cell carcinoma, and thyroid papillary carcinoma) that developed after allogeneic peripheral blood stem cell transplantation using anti-AE1/3 immunofluorescence with fluorescence in situ hybridization analysis for sex chromosomes and/or short-tandem repeat microsatellite analysis of laser-microdissected tumor cells. The results revealed that 1 of these 5 cancers was derived from donor cells. In this case, transfused pluripotent cells, which include both mesenchymal stem cells and hematopoietic stem cells, might have given rise to epithelial malignant cells. Our observations suggest that transfused peripheral blood cells may be involved in the development of cancers after allogeneic peripheral blood stem cell transplantation.     

Hematologic abnormalities following renal transplantation

Recipients of renal allografts are surviving longer and, consequently, may experience a variety of complications related not only to the transplanted kidney, but also to the hematopoietic system. Common hematologic complications in the renal transplant patient include abnormalities of one cell line, such as post-transplantation erythrocytosis or anemia, that are often treatable with simple measures. Conversely, pathologies involving the leukocyte and platelet population often exist in the context of pancytopenia, which may be a manifestation of systemic infection (e.g., cytomegalovirus, human herpesvirus 8) or malignancy (post-transplantation lymphoproliferative disorders). Uncommon, but life-threatening, processes complicating renal transplantation include hepatosplenic γδ T-cell lymphoma and viral-induced hemophagocytic syndrome, both of which are associated with severe pancytopenia and, often, death. Since this patient population is often managed in a multidisciplinary fashion by nephrologists, infection specialists, transplant surgeons, hematologists, and internal medicine physicians, a succinct review of this topic is warranted.     

移植后淋巴细胞增殖性疾病研究进展（附视频）

移植后淋巴细胞增殖性疾病是造血干细胞移植及实体器官移植后一组发生率相对较低、进展迅速、预后极差的并发症,可表现为明显的临床及病理异质性。本讲座介绍了近几年来在移植后淋巴细胞增殖性疾病发病机制和发生率、临床表现和病理诊断、移植后监测以及预防和治疗方面的研究进展。     

Continuous bladder irrigation prevents hemorrhagic cystitis after allogeneic hematopoietic cell transplantation

Hemorrhagic cystitis is 1 of the most troublesome complications of hematopoietic cell transplantation conditioning regimens. We conducted a nonrandomized controlled clinical study to investigate the role of continuous bladder irrigation in addition to mesna, hydration, and alkalization in the prevention of hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. A total of 80 eligible patients entered the study. From May 2006, 40 patients who underwent allogeneic hematopoietic cell transplantation received continuous bladder irrigation in addition to the common protocol. A historical control group of 40 consecutive patients with same inclusion criteria who did not receive bladder irrigation was enrolled from before May 2006. Hemorrhagic cystitis occurred in 50% of patients in the no bladder irrigation group versus 32% in bladder irrigation group (P = 0.11). The mean duration of hemorrhagic cystitis was significantly reduced in the bladder irrigation group (10 vs. 18 days; P = 0.02). Duration of hospitalization was significantly shorter in the bladder irrigation group (30.2 vs. 39.6; P < 0.001). Late-onset hemorrhagic cystitis that occurred beyond 4 weeks after allo-hemorrhagic cystitis happened more significantly in the no bladder irrigation group (P = 0.001). High-grade hemorrhagic cystitis was more frequently associated with high-grade graft-versus-host disease within 30 days after transplant (P = 0.06). In general, continuous bladder irrigation added to mesna, hydration, and alkalization regimens was well tolerated, decreased the complications of hemorrhagic cystitis, and may be useful in hematopoietic cell transplantation patients. However, more investigations with randomized controlled clinical trials with more patients are needed.     

Predictors of the Development of Surgical Complications among Hematopoietic Stem Cell Transplantation Recipients

Background  

This study was designed to determine possible risk factors for the development of surgical complications after hematopoietic stem cell transplantation (HSCT). HSCT carries the possibility for the development of surgical morbidities and mortalities; certain populations of patients are at higher risk for developing complications. Defining those risk factors will help surgeons to anticipate and manage these complications.     

Tolerance to vascularized kidney grafts in canine mixed hematopoietic chimeras

BACKGROUND: Recent progress in allogeneic hematopoietic stem cell transplantation provides new methods for reliable engraftment with nonlethal conditioning regimens. These techniques have been successfully applied in the treatment of both malignant and nonmalignant diseases, but have not been fully exploited for their potential to tolerize recipients for organ transplantation. These studies were undertaken to test whether the tolerance of host immune cells toward donor hematopoietic cells in mixed hematopoietic chimeras extends to include a vascularized organ, the kidney. METHODS: Using nonmyeloablative doses of total body irradiation, a short course of immunosuppression, and hematopoietic stem cells from marrow or peripheral blood sources, five dog lymphocyte antigen-identical canines were made to become stable mixed hematopoietic chimeras with no development of graft-versus-host disease or posttransplant lymphoproliferative disorder. Subsequently, renal transplantations were performed between stem cell donor and recipient littermates, and no additional immunosuppressive therapy was given after stem cell transplantation. RESULTS: All mixed chimeric dogs demonstrate different, but stable, levels of donor peripheral blood lymphocyte and granulocyte chimerism. With follow-up of longer than 1 year, all of the mixed chimeric dogs (five/five) have excellent renal function with normal serum creatinines (<1.5 mg/dl) and no pathological evidence of rejection on biopsies. CONCLUSIONS: In a major histocompatibility-matched model, minor antigen differences between donor and recipient are not sufficient to induce a host immune response to a vascularized kidney transplant in mixed hematopoietic chimeras.     

供者NK细胞及其嵌合状态在异基因造血干细胞移植中的研究进展

目前,异基因造血干细胞移植(allo-HSCT)已广泛应用于造血系统疾病的治疗,但移植术后也存在一系列并发症。NK细胞的运用为改善allo-HSCT受者预后带来希望,供者来源NK细胞通过其细胞膜上的杀伤细胞免疫球蛋白样受体与其配体错配发挥同种异体反应,该过程具有保留移植物抗白血病和减少移植物抗宿主病双重效应。NK细胞是allo-HSCT后受者体内最早重建的免疫细胞群,因此移植后供、受者NK细胞嵌合状态评估对预测疾病预后及指导干预治疗具有重要意义。基于NK细胞嵌合状态的供者NK细胞输注免疫干预疗法可改善疾病预后,在血液系统疾病治疗中表现出良好的应用前景。本文就近年来供者NK细胞及其嵌合状态在allo-HSCT中的研究进展作一综述。     

Intramyocardial CD34+ cell transplantation combined with off-pump coronary artery bypass grafting

This report describes a new therapeutic approach for severe ischemic heart disease, intramyocardial transplantation of autologous bone marrow-derived CD34 + cells combined with off-pump coronary artery bypass grafting (CABG). CD34 is widely known as a cell surface antigen expressed on hematopoietic stem cells, and recent experimental studies have shown that CD34 + cells include endothelial progenitor cells. We used the Isolex 300i magnetic cell selection system to separate CD34 + cells from bone marrow cells. This report describes the first case treated with the combination of off-pump CABG and cell transplantation for therapeutic angiogenesis and myocardial regeneration. The transplantation of autologous bone marrow-derived CD34 + cells improved perfusion of the ungraftable ischemic area.     

Bronchiolitis obliterans following hematopoietic stem cell transplantation: a clinical update

Pandya CM, Soubani AO. Bronchiolitis obliterans following hematopoietic stem cell transplantation: a clinical update.
Clin Transplant 2010: 24: 291–306. © 2009 John Wiley & Sons A/S. Abstract: Hematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant and non‐malignant conditions. Pulmonary complications, infectious and non‐infectious, are a major cause of morbidity and mortality in these patients. The recent advances in prophylaxis and treatment of infectious complications increased the significance of late non‐infectious pulmonary conditions. Currently, bronchiolitis obliterans is one of the most challenging pulmonary complications facing clinicians who are taking care of HSCT recipients. This report provides a clinical update of the incidence, risk factors, pathogenesis, clinical characteristics, and management of bronchiolitis obliterans following HSCT.     

What Risks are Associated with Primary THA in Recipients of Hematopoietic Stem Cell Transplantation?

Introduction

As patients who receive hematopoietic stem cell transplantation are at increased risk of avascular necrosis (AVN) and subsequent degenerative arthritis, THA may be considered in some of these patients, particularly as overall patient survival improves for patients undergoing stem-cell transplants. Patients receiving hematopoietic stem cell transplantation theoretically are at increased risk of experiencing complications, infection, and poorer implant survivorship owing to the high prevalence of comorbid conditions, immunosuppressive therapy regimens including corticosteroids, and often low circulating hematopoietic cell lines; however, there is a paucity of studies elucidating these risks.

Questions/Purposes

We asked: (1) What is the overall mortality of patients with hematopoietic stem cell transplantation who have undergone THA? (2) What is the complication rate for these patients? (3) What are the revision and reoperation rates and implant survivorship for these patients?

Patients and Methods

Between 1999 and 2013, we performed 42 THAs in 36 patients who underwent stem-cell transplants. Other than those who died, all were available for followup at a minimum of 2 years; of the patients whose procedures were done more than 10 years ago and who are not known to have died, two (5%) had not been seen in the last 5 years and so are considered lost to followup. All patients underwent thorough evaluation by the transplant team before arthroplasty; general contraindications included active medical comorbidities or evidence of unstable end-organ damage, active rejection, and critically low circulating hematopoietic cell lines. Underlying primary diseases leading to hematopoietic stem cell transplantation included lymphoma (14/42; 33%), plasma cell disorders (10/42; 24%), leukemia (9/42; 21%), and amyloidosis (3/42; 7%). Complications, reoperations, revisions, and implant and patient survivorship, were recorded from chart review and data from the institutional total joint registry. Mean followup was 5 years (range, 2–15 years).

Results

Patient survivorship free of mortality was 91% (95% CI, 81%–100%) and 82% (95% CI, 68%–96%) at 2 and 5 years, respectively. Complications occurred in four of 42 THAs (10%); these complications included an intraoperative fracture and a venous thromboembolism. Revisions occurred in two of 42 (5%) THAs; there were no reoperations. Implant survivorship free of component revision for any reason or implant removal accounting for death as a competing risk was 93% (95% CI, 83%–100%) at 5 years.

Conclusion

With appropriate medical evaluation and comanagement by transplant specialists, carefully selected patients with hematopoietic stem cell transplants may undergo elective primary THA, although complications do occur in this relatively fragile patient population. Although implant survivorship was modest at 93% at 5 years, there was not a high risk of revision for infection. Improved outcomes for these patients may be expected as their medical management advances and additional comparative studies may clarify other important patient factors.

Level of Evidence

Level IV, therapeutic study.

     

Renal transplantation after myeloablative and non-myeloablative hematopoietic cell transplantation from the same donor

Hematopoietic cell transplantation is a key treatment to prolong patient survival for many hematological disorders. Renal impairment is well recognized as a significant complication of hematopoietic cell transplantation, which can progress to end-stage renal disease. Herein, we report our experience of two patients who underwent renal transplantation from the same donor who provided cells for the preceding hematopoietic cell transplantation. One patient had undergone peripheral blood stem cell transplantation with a non-myeloablative conditioning regimen, whereas the other had received bone marrow transplantation with a myeloablative regimen. Chronic immunosuppressive therapy was not needed in either one to maintain the kidney graft function. Not only bone marrow transplantation with a myeloablative conditioning regimen, but also peripheral blood stem cell transplantation with a non-myeloablative regimen can confer immunological tolerance.     

Levels of anti-A/B antibodies after ABO-incompatible hematopoietic stem cell transplantation

In contrast to solid organ transplantation, ABO incompatibility is generally not associated with survival differences in hematopoietic stem cell transplantation. Therefore, patients receiving ABO-incompatible stem cell transplantation can be analyzed to study the mechanism of tolerance induction after antigen-mismatched transplantation. The goal of this study was to analyze the levels of anti-A/B antibodies after ABO-incompatible transplantation. Host-derived antidonor antibodies disappeared rapidly after transplantation and did not reappear in the further posttransplant course. Donor-derived antihost antibodies did not significantly increase and compatible anti-A/B antibodies remained positive after hematopoietic stem cell transplantation. Thus, there is no evidence for stimulation of donor B lymphocytes to produce antirecipient antibodies suggesting a potential B cell tolerance.