Acquired Aplastic Anaemia in Adults

A follow-up study of 10 patients suffering from acquired aplastic anaemia, comprising methacrylate-embedded bone marrow biopsies and CFU cultures, is presented. The haematopoietic recovery patterns and changes in the inflammatory infiltration after permanent engraftment could be distinguished from those in non-transplanted patients. After anti-thymocyte globulin treatment followed by allogeneic bone marrow infusion, the recovery pattern resembled that in non-transplanted patients. The persistently low colony-forming capacity in some patients could be explained by the existence of lymphoid inhibitory cells, which suggests an immunologic auto-destructive mechanism.     

Antibody incubation of human marrow graft for prevention graft versus host disease

Summary An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C).All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.Supported by Deutsche Krebshilfe, Bonn and Deutsche Forschungsgemeinschaft, SFB 37, B 7, E 9     

异基因骨髓移植治疗自身免疫病2例报告并文献复习

目的：通过2例自身免疫病在异基因骨髓移植后达治愈及长期缓解的病例分析和文献复习，探讨异基因骨髓移植对自身免疫病的疗效和安全性。方法：病例分析和文献复习。结果：2例骨髓移植前分别确诊系统性红斑狼疮和强直性脊柱炎的患者接受异基因骨髓移植后体内异基因骨髓均长期稳定植入，自身免疫病达完全缓解，已经分别随诊126个月和44个月。结论：自身免疫病可以由异基因骨髓移植治愈或达长期缓解。     

Discontinuation of immunosuppression for prevention of kidney graft rejection after receiving a bone marrow transplant from the same HLA identical sibling donor

Induction of tolerance in solid organ transplant recipients has been a long sought goal so that patients will not need lifelong immunosuppression. In this case report we review a patient who received a kidney transplant from an HLA matched related sibling and developed acute leukemia as a consequence of her immunosuppression. The patient was then treated with an allogeneic bone marrow transplant from her kidney donor. After the bone marrow transplant, all immunosuppression therapy for graft rejection and graft versus host disease was stopped. Six months after the bone marrow transplant, the patient's kidney function had no deterioration as a consequence of stopping immunosuppression. This illustrated that a combined solid organ/bone marrow transplant can help to induce tolerance. In fact, the tolerance to the bone marrow transplant for prevention of graft versus host disease may have been accomplished by the prior kidney transplant.     

Bone marrow morphology during alpha-interferon treatment in hairy cell leukemia

14 patients with HCL were started on alpha-interferon (IFN) treatment. Bone marrow changes were followed in trephine biopsies every 3rd month. Differential counting was performed according to the point counting method and fiber content was evaluated. At the start of treatment all patients had 80% or more of tumor cells in the bone marrow. The reduction of granulopoiesis was more pronounced than for erythropoiesis. During treatment cellularity decreased in 6/13 patients already after 3 months; later, cellularity was normalized in most patients. Only 1 patient showed a complete remission. 12/14 patients showed a significant but slow reduction of tumor cells. Also, between 12 and 18 months an improvement was seen in some patients. The megakaryocytes improved rapidly and the erythropoiesis was normalized before the granulopoiesis. Only 1 patient did not show a bone marrow response. 5/14 patients showed a reduction of bone marrow fibers, first seen after 6 months of treatment. IFN was discontinued in 9/14 patients. 7 of these relapsed during the observation period (18 months).     

Autologous bone marrow transplantation for intra-abdominal extramedullary plasmacytoma

Summary A patient with an extramedullary plasmacytoma of the omentum and ovaries is described. In spite of the presence of a very high concentration of paraprotein (103.5 g/l IgG k), bone marrow involvement was not demonstrated either at presentation or during the course of the disease. After debulking surgery, chemotherapy (vincristine, prednisone, and cyclophosphamide) was initiated. Although this resulted in considerable improvement, the paraproteinemia persisted. After ten courses of chemotherapy there was recurrence of the tumor with involvement of the lymph nodes in the right axilla. Chemotherapy was changed to a CHOP regimen (cyclophosphamide, adriamycin, vincristine, and prednisone), followed by autologous bone marrow transplantation with the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) as conditioning therapy. The patient was still in complete remission 1 year after transplantation. This case demonstrates that an extramedullary plasmacytoma may become manifest as extensive but localized disease with high levels of paraprotein, and that autologous bone marrow transplantation as a therapeutic modality can lead to prolonged complete remission of the disease.     

Complete remission of tumour with interleukin 2 therapy in a patient with non-Hodgkin's lymphoma post allogeneic bone marrow transplant associated with polyclonal T-cell bone marrow lymphocytosis

A patient with low-grade non-Hodgkin's lymphoma (NHL) who relapsed shortly after an allogeneic bone marrow transplant (BMT) is reported. The patient was treated with interleukin 2 (IL-2), which resulted in a flare-up of graft-versus-host disease followed by disease control, with disappearance of peripheral lymphadenopathy. Sequential bone marrow testing showed the disappearance of bone marrow involvement with disease but occurrence of T-cell aggregates post IL-2 that were identified as polyclonal by molecular methods. The patient remains in complete remission 37 months following allogeneic BMT.     

Allogeneic bone marrow transplantation for severe aplastic anaemia-the London experience

Using the Seattle protocol with minor modifications, 23 patients with severe aplastic anaemia received allogeneic bone marrow transplants from HLA/ mixed leucocyte culture matched sibs in three London centres between 1973 and 1977. Ten patients (43.5%) are alive 6 months to 5 years after transplantation, and are well with full haemopoietic reconstitution, two with autologous bone marrow recovery following the graft procedure. A failure of the marrow graft to take, or take followed by rejection occurred in 12 patients (52%). Failure of marrow recovery was associated with a high early mortality from bacterial or fungal infection. The only survivors amongst those who rejected the first graft were four patients in whom a subsequent graft from the same donor was successful, and two in whom autologous recovery occurred. Graft versus host disease (GVHD) occurred in seven patients, and was fatal in one case. The most frequent complication after successful engraftment was varicella-zoster infection which occurred in five patients and was fatal in one patient. The overall results compare favourably with those from other transplant centres, but the high rate of graft rejection and low incidence of GVHD differ from other series. The results should encourage further referral of patients with severe AA for bone marrow transplantation.     

Secondary leukemia after severe aplastic anemia

Summary We describe a patient with acute myeloid leukemia (AML) occurring 5 years after successful treatment of severe aplastic anemia (SAA) with antilymphocyte globulin (ALG). Four years after ALG, SAA had relapsed. A second remission of SAA was achieved, but was followed by transformation of the myelodysplastic syndrome into overt AML. After 2 courses of high-dose cytosine arabinoside and VP-16 complete remission occurred. This case shows that chemotherapy of secondary leukemia after SAA is feasible, and that ex-aplastic bone marrow is capable of complete recovery from chemotherapy-induced aplasia. Morphological anomalies of bone marrow noticed early during remission of SAA might predict a late transformation in leukemia.     

自体骨髓移植结合强烈化疗治疗急性白血病疗效观察

为探讨减少自体骨髓移植（ABMT）后复发率和延长无病生存期。作者采用ABMT结合强烈化疗的方法治疗急性白血病。能列入统计的12例患者中,8例移植后已持续完全缓解19～79个月,中位数58.5个月。证明采用ABMT结合强烈化疗方法,可以减少急性白血病的复发率和延长无病生存期。     

Metastasis of Solid Tumors in Bone Marrow: A Study from Northern India

The metastasis of bone marrow by the solid tumors is a sign of advanced stage of disease and poor prognosis. The aim of this study was to assess the pattern of bone marrow involvement of different solid tumors and their correlation with hematological findings. In a retrospective study we evaluated 434 aspirates and 76 biopsy sections from 124 cases of different types of solid tumors previously diagnosed on the basis of their clinical and histopathological findings. The hematological profile of the patients was done and correlated with the bone marrow findings. The study was carried out at a medical college hospital of northern India. Out of 124 cases of solid tumors 31 (25%) have metastasized to bone marrow. The highest number 25 (36%) of bone marrow involvement was seen in carcinoma prostate followed by gastric carcinoma and melanoma (25%) The least number (14.2%) cases of bone marrow metastasis were observed in endometrial carcinoma. Anemia was found the commonest (71.4%) hematological finding followed by thrombocytopenia in 45.1% cases. The bone marrow examination is an easy, convenient, sensitive and cost effective procedure for assessment of staging and monitoring of prognosis of solid tumors.     

自体骨髓干细胞移植治疗肝衰竭的初步观察

目的观察自体骨髓干细胞移植治疗肝衰竭的初步疗效。方法 12例经常规内科综合治疗无明显效果的肝衰竭患者。在无菌条件下采集骨髓100～200ml,通过密度梯度离心分离纯化出骨髓干细胞,通过介入的方法经肝动脉注射入肝内,静脉输注肝细胞生长素1～2周。观察移植后1、2、3和6月患者症状、体征、肝脏生化和凝血酶原时间等的变化。结果 9例肝衰竭患者的症状、体征改善,白蛋白升高、胆红素降低,肝脏功能改善,所有患者未见明显副作用。结论自体骨髓干细胞移植治疗肝衰竭安全有效。     

Allogeneic bone marrow transplantation for high risk non-hodgkin's lymphoma during first complete remission

Summary Allogeneic bone marrow transplantation from histocompatible sibling donors was performed in six patients with extranodal involvement of high grade lymphoma during first complete remission. Five patients had lymphoblastic lymphoma and one had diffuse undifferentiated lymphoma. The cytoreductive/immunosuppressive regimen consisted of total body irradiation and high dose cyclophosphamide. Four patients are alive in complete remission at 8 months, 14 months, 21 months and 47 months post transplantation. One patient who relapsed 7 months after his initial transplantation underwent a second transplantation but another relapse 17 months later led to his death. One patient died of chronic graft-versus-host disease and at autopsy there was no evidence of lymphoma. These data demonstrate that allogeneic bone marrow transplantation can produce durable remissions in patients with high grade lymphoma who present with bone marrow, central nervous system and/or skin involvement.     

A second course of treatment for childhood acute lymphoblastic leukaemia: long-term follow-up is needed to assess results

We report the results of long-term follow-up of 94 children who completed treatment for acute lymphoblastic leukaemia (ALL) between 1974 and 1986 and subsequently experienced a bone marrow relapse before 1992. 91 children received further induction, intensification and CNS directed therapy; 19 proceeded to BMT or ABMT and the remainder were treated on one of three protocols which increased in intensity. The duration of second remission improved significantly with increasing intensity of treatment and bone marrow transplantion was followed by fewer relapses than chemotherapy. Analysis of factors influencing the duration of second remission showed that only length of first remission was of additional significance; the median duration of second remission being only 19 months in children with a first remission of less than 4 years and 62 months in those with longer first remissions. 29 children electively stopped chemotherapy a second time but only 11 of these remain still in second remission with recurrences occurring for up to 7 years from the the time first relapse. Only three of the 24 longterm survivors had no significant late effects of treatment; these were most marked in children who had received a second course of radiotherapy. We conclude that very long follow-up is necessary to determine whether patients may be successfully re-treated following late bone marrow relapse and that all such treatment is associated with a high incidence of late effects.     

Successful allogeneic bone marrow transplantation after reversion to chronic phase of blast crisis in chronic myeloid leukemia

A female with chronic myeloid leukemia (XX Ph 1 +) in blast crisis (localized to pleura and lymph nodes) was treated by polychemotherapy. After reversion to the chronic phase, an allogeneic bone marrow transplantation (BMT) was performed. Sixteen months after BMT, no sign of the disease was present (XY Ph 1 -).     

Retroviral-mediated gene transfer into human bone marrow stromal cells: Studies of efficiency and in vivo survival in SCID mice

Abstract: Retroviral-mediated gene transfer into bone marrow cells is extensively used in gene therapy protocols. Cytokines are needed for stimulation, to achieve a high rate of gene transfer. However, the stromal cell compartment of bone marrow is characterized by rapid proliferation even without cytokines. In this study, human bone marrow stromal cells were isolated and subsequently infected with recombinant retrovirus in a cell-free supernatant. The LN retroviral vector used in this study carries the bacterial neomycin phosphotransferase gene (neoR). Transduction efficiency was significantly enhanced by repeated cycles of infection, with a maximum of 91% transduced cells by four rounds of infection. Presence of the neoR-gene was detected by PCR from all stromal cells selected by G418. After culture in vitro for 3 months, cells were still positive for PCR amplification of the neoR-gene. Transduced stromal cells were also injected into SCID mice to study their homing and survival ability in vivo.     

Massive plasmocytosis due to methimazole-induced bone marrow toxicity.

Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.     

骶尾部藏毛窦术后复发并发骶尾骨骨髓水肿一例

探讨骶尾部藏毛窦术后复发并发骶尾骨骨髓水肿的治疗效果，术后给予抗生素及抗厌氧菌药物治疗，术后换药，骶尾部伤口于术后24天愈合，术后42天复查MR，骶尾骨骨髓水肿明显消退，随访1年，患者无不适，骶尾骨未见骨髓水肿。     

High dose busulfan/etoposide as a preparatory regimen for second bone marrow transplants in hematologic malignancies

Summary Five patients with hematologic malignancies who had relapsed between seven months and eight years after their primary bone marrow transplants were prepared with high dose busulfan/etoposide for second marrow transplanatations from the same donors who had provided the marrow for the primary transplants. The preparatory regimen was well tolerated. All patients engrafted and entered complete remission. Two patients are alive and in continued remission two and ten months after second transplant. One patient died with acute respiratory failure after two months and two patients relapsed again eight and 17 months after second marrow transplantation. The combination busulfan/etoposide may prove to be a suitable preparatory regimen for second bone marrow transplant attempts in selected patients.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.