Antibody-mediated marrow failure after allogeneic bone marrow transplantation

Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft failure, either by antibody-dependent cell-mediated cytotoxicity (ADCC), or complement- mediated cytotoxicity. In the case of HLA Class I disparity, where all donor cells express the target antigen, the presence of alpha-donor antibody was associated with complete graft failure and death. In the case of ABO blood group antigen disparity, the presence of alpha-donor antibody resulted in erythroid hypoplasia. The latter cases proved informative insofar as they established that host antibodies could persist for more than 18 months after chemoradiotherapy and impair marrow function.     

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation

We describe a patient who developed Aspergillus tracheobronchitis after BMT. She complained of progressive dyspnea on day +165 and her respiratory function deteriorated rapidly. Although neither early chest X-rays nor CT scans were negative, bronchoscopy revealed formation of a pseudomembrane around the bronchial walls. Based upon pathological and microbiological examinations, she was diagnosed as having invasive Aspergillus tracheobronchitis. Retrospectively analyzed, the Aspergillus circulating antigen detection tests became positive before clinical symptoms developed, and may be beneficial for early diagnosis of Aspergillus tracheobronchitis. This form of aspergillosis should be regarded as one of the serious complications after BMT.     

Hepatopulmonary syndrome after allogeneic bone marrow transplantation

A 10-year-old girl with aplastic anemia received an allogeneic bone marrow transplantation (BMT). Three years after an uneventful course apart from chronic graft-versus-host disease (GVHD) she presented with chronic hypoxemia, reduced diffusion capacity of the lungs, normal spirometric lung function and increased bilirubin and liver enzymes. Intrapulmonary vascular dilatations were demonstrated. Pulmonary complications after BMT may include a hepatopulmonary syndrome (liver disease, hypoxemia, intrapulmonary vascular dilatations).     

Eosinophilic fasciitis after allogeneic bone marrow transplantation

We describe a patient with eosinophilic fasciitis (EF) developing 8 months after an allogeneic bone marrow transplantation for acute myeloblastic leukemia. The patient responded to low dose prednisone. A full thickness skin-muscle-fascia biopsy detected the characteristic fascial changes of EF and distinguished it from other forms of chronic graft-versus-host-disease (GVHD). This distinction may be important since EF after bone marrow transplantation may occur more often and it may respond to treatment with low doses of prednisone whereas chronic GVHD usually requires more extensive immunosuppressive treatment.     

Late complications after allogeneic bone marrow transplantation for leukaemia

Late effects of bone marrow transplantation are of clinical concern as more patients survive the early phase after transplantation and remain free of their original disease. Late effects express themselves as structural or functional impairment of organs or tissues or as neoplastic growth secondary to the primary treatment. Non-neoplastic late effects affect growth and development of children, endocrine and reproductive function, and the function of eyes, lungs, kidneys and other organs. Secondary neoplasms comprise malignant lymphoma and leukaemia, many of them in donor cells, that occur early after transplantation. The incidence of solid tumours is increased years after transplantation. At present the risk of secondary neoplasms after transplantation appears not to be different from that of intensive chemoradiotherapy without transplantation. In contrast to conventional chemoradiotherapy secondary malignancies of the host's haemopoiesis are rare due to the myeloablative conditioning. The incidence of solid tumours may increase as more patients survive more than a decade after transplantation.     

Functions of granulocytes after allogeneic bone marrow transplantation

Summary The phagocytosis and intracellular killing by granulocytes as well as the opsonizing capacity of the serum were studied in 13 patients who had undergone allogeneic bone marrow transplantation. Phagocytosis was normal in all patients. A moderately impaired opsonic activity of the serum was found in two patients, who were investigated within 30 days after the transplantation. The intracellular killing was less than control values in two patients. In one patient this was probably due to the existence of a split chimerism.Supported by a grant of the J. A. Cohen Institute, Leiden, The Netherlands     

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).     

Granulocyte colony-stimulating factor after allogeneic bone marrow transplantation

Hematopoietic growth factors have been shown to be effective in reducing the period of neutropenia after autologous bone marrow transplantation (BMT). Initial concerns over potential aggravation of graft-versus-host disease (GVHD) and increase in the incidence of relapse in patients with myeloid leukemias influenced the number of studies using hematopoietic growth factors after allogeneic BMT. We report the experience with 50 patients treated at a single institution using granulocyte colony-stimulating factor (G-CSF) after allogeneic sibling (n = 30) and matched unrelated (n = 20) BMT. The time to an absolute neutrophil count > or = 500/microL was significantly faster in patients who received G-CSF and cyclosporine and prednisone for GVHD prophylaxis when compared with historical control patients receiving the same GVHD prophylaxis (10 v 13 days, P < .01). A similar accelerated myeloid engraftment was observed for those patients who received the addition of methotrexate for GVHD prophylaxis when compared with historical control patients receiving the same GVHD prophylaxis regimen (16 v 19 days, P < .05). The median time to engraftment for patients receiving a matched unrelated BMT and G-CSF was 17 days (range 13 to 26). We did not observe any increase in GVHD or early mortality in the matched related sibling BMT. The incidence of acute GVHD in the matched unrelated BMT recipients was also low at 21%; however, 9 patients (45%) died within 100 days of the date of BMT, similar to the experience reported with granulocyte-macrophage CSF. This study confirms the efficacy of G-CSF in accelerating myeloid engraftment after allogeneic matched sibling BMT. The higher early mortality associated with patients receiving matched unrelated BMT suggests that randomized controlled trials using G-CSF after allogeneic BMT should be performed.     

Mycobacterial pulmonary infections after allogeneic bone marrow transplantation

Allogeneic bone marrow transplant recipients are prone to pulmonary infections caused by a wide spectrum of organisms. Nonetheless, the recognition of lung disease caused by Mycobacterium tuberculosis in two patients and Mycobacterium avium-intracellulare in a third patient at the University of Texas M. D. Anderson Hospital represents the first report of these agents occurring in allogeneic marrow recipients. Diagnosis can be difficult due to atypical presentations, initial negative culture results, and the presence of more than one pathogen in these compromised hosts. In the case involving Mycobacterium avium-intracellulare infection, culture of material obtained by bronchoscopy established the diagnosis when repeated sputum samples showed no growth. A vigorous search for mycobacteria is suggested in allogeneic bone marrow transplant recipients with pulmonary infections.     

Drug-induced liver injury after allogeneic bone marrow transplantation

A 23-year-old woman developed acute severe hepatitis and jaundice on day 183 after bone marrow transplantation from HLA-B antigen mismatched-related donor. The administration of prednisolone and cessation of the prescribed drugs resolved the liver injury. Drug lymphocyte stimulation test was positive for acyclovir, and liver biopsy indicated the characteristics of drug-induced liver injury (DILI) rather than graft-versus-host disease. Physicians should keep DILI in mind when considering differential diagnosis for liver complications after allogeneic cell transplantation.     

Acquired autoimmune thrombocytopenia after allogeneic bone marrow transplantation

A 29-year-old man in remission from acute myeloblastic leukaemia was treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from his HLA identical brother. Engraftment was documented on D12. Transient acute GVHD (grade II) appeared from D34. No infection complicated the BMT. Nevertheless severe thrombocytopenia persisted and was unresponsive to marrow donor platelet transfusion. The platelet immunofluorescence test demonstrated the autoimmune basis of the thrombocytopenia. This study suggests that the transient immune imbalance observed in the early post graft period could facilitate the appearance of autoimmune cytopenias.     

Diffuse alveolar hemorrhage after allogeneic bone marrow transplantation

A 34-year-old woman with chronic myeloid leukemia underwent allogeneic bone marrow transplantation (BMT) after receiving high-dose chemotherapy and total body irradiation. She experienced progressively dry cough 51 days after BMT, and chest X-ray films showed patchy infiltrations in the lower fields of both lungs on the 66th day after BMT. The symptoms of cough, fever, and hypoxemia worsened. The patchy infiltrations continued to spread and fuse. Diffuse alveolar hemorrhage (DAH) was diagnosed on the basis of high-resolution CT and bronchoalveolar lavage findings. Treatment with high-dose methyl prednisolone pulse therapy, antibiotics, and haptoglobin resolved the patient's DAH symptoms. DAH was thought to be secondary to thrombotic microangiopathy. The majority of patients who experience DAH after BMT eventually die. The remission observed in our case was rare, and illustrated that steroid therapy can be effective for DAH after BMT.     

Malignant fibrous histiocytoma after allogeneic bone marrow transplantation

A 24-year-old woman with CML underwent allogeneic BMT in August 1995 from a one-antigen HLA mismatched brother. Conditioning included BuCy2 and CsA and MTX were used to prevent GVHD. In July 1997 she developed right leg pain, lytic bone lesions of distal femur and a solid mass of soft tissue. Histological diagnosis of malignant fibrous histiocytoma was made. Despite treatment with surgery and chemotherapy (doxorubicin and ifosfamide), the patient died 1 year later with local recurrence of the tumor and liver, lung and brain metastases. The CML was in CR.     

Polyclonal reconstitution of human marrow after allogeneic bone marrow transplantation

Clonal dominance suggestive of reconstitution of marrow from small numbers of pluripotent hematopoietic stem cells has been noted in different experimental and clinical situations. Recipients of human allogeneic marrow transplants have not been previously studied to determine if clonal dominance occurs in this clinical setting. Clonal analysis of 20 allogeneic marrow transplant recipients was performed on DNA from peripheral blood neutrophils using restriction fragment length polymorphisms on the X chromosome. Similar studies were performed on 16 of the donors. To analyze the results further, recipients were paired with their respective donors. There was no evidence of shifts in cell populations contributing to the X chromosome inactivation patterns in recipient marrow grafts when compared with their respective donors. A mathematical model based on binomial statistics was adapted to estimate the numbers of reconstituting pluripotent hematopoietic stem cells. There was no evidence of clonal dominance suggestive of oligoclonal reconstitution in marrow grafts after allogeneic marrow transplantation. This does not preclude the possibility of oligoclonal reconstitution in other marrow transplant settings such as autologous transplantation.