Marmont Am

Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT* SAA Working Party

This is an analysis of 509 patients with severe aplastic anaemia (SAA) treated in Europe between 1981 and 1986; 218 patients were treated by allogeneic bone marrow transplantation (BMT) from HLA identical sibling donors and 291 with immunosuppressive therapy (IS) with antilymphocyte globulin (ALG). The overall actuarial survival was 63% after BMT and 61% after IS therapy at 6 years. All patients fulfilled the criteria of SAA; however, most patients with a neutrophil count of <0.2 × 109/l also had infections and haemorrhages. Therefore a further subclassification was defined by pretreatment peripheral blood neutrophil count: very severe aplastic anaemia (vSAA) (<0.2 × 109/l neutrophils) and moderately severe aplastic anaemia (mSAA) (0.2‐0.5 × 109/l neutrophils).

Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration

A 46 year woman with severe long-lasting SLE received an autologous bone marrow transplantation utilising CD34+ haematopoietic progenitors following a 3 log T-lymphocyte depletion. The immunosuppressive regimen (conditioning) consisted of 15mg/kg Thiotepa followed by 100 mg/kg of cyclophosphamide over 2 d. Granulocytic recovery was aided by G- CSF. The post-transplant course was uneventful, and a good clinical and immunologic remission (ANA negativisation) was achieved. This is the first case of SLE having received an autologous progenitor cell transplant for the autoimmune disease by itself, unaccompanied by a haematologic condition requiring transplantation. The potential, advantages and limits of this procedure, which are currently being explored worldwide, are briefly discussed.

Abo Compatibility And Acute Graft-versus-host Disease Following Allogeneic Bone Marrow Transplantation

If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n=32) or leukemia (n=142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P=0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P=0.06), older recipients age (P=0.08), fast engraftment (P=0.03), and older donors age (0.08) were also associated with a higher risk of GVHD. Recipients ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P=0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P=0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.

Adoptive autoimmune hyperthyroidism following allogeneic stem cell transplantation from an HLA-identical sibling with Graves' disease.

Autoimmune diseases which follow allogeneic BMT from a donor who is a patient or a carrier of an autoimmune condition are considered to be a paradigm of adoptive autoimmunity. Seven cases of autoimmune thyroiditis associated with clinical hyperthyroidism have been published to date. In the case reported here a 35-year-old female patient with AML of the M2 subtype received unmanipulated PBSC from her HLA-identical sister who had therapeutically controlled Graves’ disease. Antithyroid antibodies, including thyrotropin receptor (TSHR) antibodies, appeared 1 year after transplant. Clinical hyperthyroidism requiring thyrostatic medication appeared after 2 years. The biological and clinical implications of adoptive, post-transplant autoimmunity are briefly discussed.

Predictability before transplant of hepatic complications following allogeneic bone marrow transplantation.

This study was undertaken to evaluate the occurrence of VOD and other liver diseases following BMT in a patient population with a high incidence of hepatitis before conditioning regimen. We prospectively reviewed 186 consecutive patients undergoing BMT from 1976 to 1986 to determine incidence and type of liver disease after BMT and predisposing factors. Two of 186 patients experienced VOD (1.07%). Acute and chronic liver GVHD were found in 25.8% and 36% of the patients, respectively. Acute hepatitis (AH) was diagnosed in 29.4% and chronic hepatitis (CH) in 42.6% of the patients. Statistical analysis showed no influence of pre-transplant variables on the occurrence of acute GVHD and AH; there was a weak correlation (P=0.01) between pre-BMT abnormal transaminases and occurrence of chronic GVHD. Contingency table and Cox analysis showed a greater risk of CH for patients with abnormal pretransplant SGPT levels (P=0.0004 and P=0.0022). No other variables could be associated with posttransplant CH. Actuarial survival was 71% versus 69% for patients with normal versus abnormal transaminases (P = 0.2). As VOD was a rare event, despite 53% of patients having abnormal transaminase values before transplant, we suggest that a lower and slower TBI is more important than pretransplant normal transaminases in preventing this complication. We conclude that evidence of compensated hepatitis is not a relative contraindication for BMT.

Failure of autologous stem cell transplantation in refractory thrombocytopenic purpura

A 44-year-old man with splenectomised refractory autoimmune thrombocytopenic purpura (AITP) of 10 years’ duration underwent an autologous, T cell-depleted marrow transplant following conditioning with thiotepa and CY. There was no response to the transplant procedure. This is the fourth case in the literature to show failure following autologous stem cell transplantation, although complete, steroid-independent remissions were obtained in the first two patients for over 1 year.

Fractionated total body irradiation in marrow transplantation for leukaemia

Summary. Thirty consecutive patients with leukaemia were prepared for bone marrow transplantation (BMT) with cyclophosphamide (CY) 120 mg/kg followed by total body irradiation (TBI). TBI was delivered in a single dose (sTBI) of 10 Gy, at a dose rate of 0·06–0·08 Gy/min, or in fractionated doses (fTBI) of 3·3 Gy/d, on each of 3 consecutive days, at the same dose rate. Lung shielding was adopted for all patients, in order to obtain a homogeneous dose delivered to the lung and at midline. The first 12 patients were prepared with sTBI and the following 18 with fTBI.

Autologous stem cell transplantation for severe autoimmune diseases: a 10-year experience.

Abstract:  The first autologous hematopoietic stem cell transplantation in Europe for a patient with severe refractory systemic lupus erythematosus (SLE) was performed in Genoa in 1996. Since then, 32 patients with a wide spectrum of autoimmune diseases (ADs) received autologous transplants, 22 of them with multiple sclerosis (MS). There were no fatal adverse events. All patients had complete or very good partial remissions, but relapses were frequent, especially in SLE, though never as aggressive as pretransplant. The mechanism of action of this intervention remains not completely understood, as briefly discussed here.

Autologous and allogeneic bone marrow transplantation in acute myeloid leukemia in first complete remission: an update of the Genoa experience with 159 patients

SummaryIn the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy × 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was “purged” with in vitro technique, this review seems to confirm the importance of “in vivo” purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to drow final conclusions.

Hairy Cell Leukemia: A Retrospective Study of 235 Cases by the Italian Cooperative Group (ICGHCL) according to Jansen’s Clinical Staging System

This is a report from a cooperative study on hairy cell leukemia (HCL) involving 20 Hematology Departments in Italy. Data for the patients was collected between January 1967 and December 1981 and included 235 cases of which 203 could be evaluated; 160 were males (78.8%) and 43 females (21.2%) with an M:F ratio of about 3:1; mean age was 54 years (range 26-82 yrs). The diagnostic criteria of admission were: typical aspect of hairy cells, in peripheral blood and bone marrow smears, tartrate resistant acid phosphatase (TRAP) positivity, typical bone marrow, spleen, liver and/or lymph node histology, and/or electronmicroscopy. On the basis of hemoglobin level and spleen size at the time of diagnosis, three stages could be distinguished according to Jansen: 51 patients, 27 of which splenectomized, were in stage I; 67 patients, of which 44 splenectomized, were in stage II; 85 patients of which 60 splenectomized, were in stage III. The actuarial survival curves of these patients showed clear distinction between the three stages. In the first stage the difference in survival, between splenectomized and nonsplenectomized groups, was not statistically significant (p less than 0.5): on the contrary, in stages II and III the difference in survival was statistically significant (stages II and III; p less than 0.01).