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Forty successful marrow grafts have been carried out since April 1972 for the treatment of severe refractory aplastic anemia or acute leukemia. All patients were HL-A identical and nonreactive in mixed leukocyte culture tests with the marrow donor. Nineteen of the patients developed moderately severe to severe graft-versus-host disease (GVHD) and were treated with rabbit or goat antihuman antithymocyte globulin (ATG). Under ATG therapy, 12 of the 19 showed complete resolution of GVHD, five showed improvement of most organ systems involved, and two showed no change except for improvement in skin lesions. Six of the 19 became long-term survivors. Five of the six are alive between 276 and 629 days after grafting, and one died on day 346 with chronic respiratory failure. Of the remaining 13 patients, 11 died with interstitial pneumonitis of predominantly viral etiology, and two died with fungal and bacterial infections. In conclusion, the present study demonstrates the relative effectiveness of ATG in reversing human GVHD. Death with interstitial pneumonitis was the single most serious impediment to successful treatment of GVHD by ATG.

Skin biopsies from 6 patients with chronic graft-versus-host disease (GVHD) were studied ultrastructurally. The 6 patients experienced an early lichenoid phase 65-135 days after the graft and 3 of them progressed to a late sclerotic phase 200-340 days after the grafting Damage to the basal membrane and to the keratinocytes of the basal layer and low spinous layers, and presence of epidermal regenerative cells were features common to the lichenoid phase of chronic GVHD and idiopathic lichen planus. The late sclerotic phase of GVHD with persistence of basal cell injury, normal periodicity and structure of the collagen fibres and numerous active fibroblasts in the upper third of the dermis were findings that distinguished GVHD from scleroderma. Satellite cell necrosis, i.e. lymphocyte satellites of necrotic keratinocyte, was observed in the two phases of chronic GVHD. Thus at the ultrastructural level the early phase of chronic GVHD mimics lichen planus, but the late sclerotic phase is distinct from scleroderma.

Bone marrow transplantation (BMT) is currently used to treat patients with severe aplastic anemia or leukemia. Despite the use of an HLA identical sibling donor, however, the survival after BMT is reduced by the occurrence of two major immunologic complications: graft-vs-host disease and a long-lasting immune deficiency responsible for late infections. This immune deficiency could be explained by an imbalance of lymphocyte subpopulations reconstituted after transplant. The aim of the present work was to study the helper function by measuring the production of interleukin 2 (IL 2). This lymphokine is responsible for the amplification of the effector phase of immunity. A consecutive series of 34 patients was tested for IL 2 production after BMT. This production was absent or low in 32 of 34 patients for at least 2 yr after BMT. The mechanism of this low IL 2 production was investigated. Irradiation of patients' lymphocytes in vitro with low dose gamma-rays partially restored the IL 2 production after 6 mo of evolution. The IL 2 production was not restored or was slightly affected by irradiation early after BMT. These results suggest that the lack of immune reconstitution after BMT may be caused by the lack of IL 2-producing cells and/or the increased activity of suppressor cells of the helper function. This suppression is radiosensitive.

Resume Dans notre serie historique de 60 patients greffes pour une aplasie medullaire grave ou une leucemie aigue, 30 % des malades presentent une infection fongique, lethale dans 12 cas. 67 patients ont recu un traitement prophylactique des infections fongiques par le ketoconazole. Ce traitement dont les posologies varient de 6 mg a 18 mg/kg est commence des le conditionnement et est poursuivi tant que persiste le deficit immunitaire. A ce traitement est associe un isolement en chambre sterile a flux laminaire et une decontamination digestive totale par des antibiotiques non absorbables. Aucun effet secondaire net peut etre attribue au ketoconazole dont la tolerance est excellente. La decontamination fongique de la gorge est obtenue chez 57 % des patients mais l'absence d'isolement fongique des selles n'est constatee que chez 12 % des greffes. Une infection systemique n'est observee que dans 4 cas (6 %). Si l'absorption du ketoconazole est diminuee apres greffe, les concentrations restent satisfaisantes sauf en cas de reaction severe du greffon contre l'hote.

Transplant outcome was analyzed in 690 recipients of bone marrow transplants (BMTs) for acute lymphoblastic leukemia (ALL) in first (n = 299) or second remission (n = 391). Actuarial 5-year leukemia-free survival was 42% +/- 9% (95% confidence interval) and 26% +/- 6%, respectively; relapse rates were 29% +/- 9% and 52% +/- 8%, respectively. Five-year leukemia-free survival was 56% +/- 18% in children and 39% +/- 10% in adults (P less than .02) transplanted in first remission. In first-remission adults, non-T-cell phenotype, male to female donor-recipient sex-match and graft-v-host disease (GVHD) were associated with decreased leukemia-free survival; inclusion of corticosteroids in the regimen to prevent GVHD was associated with increased leukemia-free survival. Variables associated with decreased leukemia-free survival after second-remission transplants were age greater than or equal to 16 years and relapse occurring while on therapy. Variables associated with increased probability of relapse were similar for first- and second-remission transplants and included GVHD prophylaxis without methotrexate and absence of GVHD. In first- remission transplants, leukocyte count greater than or equal to 50 x 10(9)/L at diagnosis was also associated with increased relapse; in second remission, relapse while receiving chemotherapy was also associated with increased posttransplant relapse. These data emphasize the importance of both disease- and transplant-related variables in predicting outcome after BMT. They may be used to explain differences between studies, design future trials, and identify persons most likely to benefit from BMT.

Summary. This is a report of the European Group of Bone Marrow Transplant (EGBMT) on the influence of immunosuppression (IS) on survival of patients with severe aplastic anaemia (SAA). Fourteen teams participated in this survey involving 170 cases treated from 1974 to December 1980. The 1 year survival was 62.7%. Three types of treatment were used: (1) anti-thymocyte globulin (ATG) alone, (2) anti-thymocyte globulin and haplo-identical related bone marrow infusion, and (3) high dose bolus-6-methyl-prednisolone (b-6 MePr). There was no statistical difference in survival between these three groups. Androgens did not modify survival. Blood counts before treatment had a significant prognostic value. Patients with less than 0.2 x 109/l granulocytes and less than 10 x 109/l reticulocytes had 40% 1 year survival; the others had more than 70% 1 year survival. Patients with complete or partial reconstitution had the same good prognosis. In contrast, patients with no improvement after IS had a 27% 1 year survival. Several successive courses of IS improved the prognosis of non-responding patients. This survey confirms that IS improves the survival of patients with SAA. A prospective study will be performed to define the best and safest form of IS and to correlate clinical results with in vitro tests.

Central venous catheters (CVC) have proven to be a reliable route of the administration of chemotherapy, saline, blood cells and nutritional support in patients with malignant haematological disease. However, infection remained one of the most important causes of morbidity associated with this procedure. The aims of this study were a) to evaluate the efficacy of laminar air flow to prevent CVC infections, b) to study morbidity associated with polyethylene (PE) and silicone (S) catheters, and c) to evaluate the part played by increasing staff practice. 177 CVC were inserted in 170 children during a period of 20 months. Ages ranged from 5 months to 15 years (mean: 7 years). All the S CVC were tunnelled whereas, because of their rigidity, none of the PE CVC were. At the time of their removal, bacteriological samples from the CVC skin exit site, blood drawn through the catheter and the tips of these CVC were cultured. During the first period (one year), three groups of CVC were studied: in group 1, 37 S CVC in patients placed in a non-sterile ward; in group 2, 40 S CVC in children nursed under laminar air flow; in group 3, 60 PE CVC in patients of a non-sterile ward. During the second period (8 months), 40 new S CVC were inserted in children nursed in non-sterile wards, but after nursing staff training (group 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Summary CMV infection is one of the major infection after bone marrow transplantation. CMV viremia was systematically studied in 66 patients with aplastic anemia or leukemia undergoing BMT. 57% patients had CMV viremia with a frequency peak between 7 and 9 weeks after transplant. Clinical symptoms found during viremia were pancytopenia, fever, cytolytic hepatitis. Interstitial pneumonitis was found only in 4 cases. In 3 cases, viremia was not associated with clinical symptoms. Survival was identical to the group of patients without viremia. Viremia was positively associated with the presence of high anti-CMV antibody titer in donor or recipient before transplant, or to a lymphocyte proliferative response against CMV antigens in donor or recipient before BMT. Granulocyte transfusions increased the frequency of CMV viremia. CMV infection was significantly associated with acute and chronic graft versus host disease. The relation showed between these parameters and viremia provides a basis for an accurate diagnosis of CMV infection and a better background for the study of prophylactic or curative treatment of CMV infection.

Bone marrow transplantation using an HLA-MLC-identical sibling is the most valuable treatment of severe aplastic anemia.2,6,7 Between November 1973 and March 1977, 25 consecutive patients have been treated by marrow transplantation in our unit. Nine patients are alive with complete hematologic restoration between 3 months and 3 years. The high mortality can be largely accounted for by marrow graft rejection (14 patients). Despite the small number of patients, we have tried to identify prognostic factors associated with marrow graft rejection. They are mainly the existence of anti-HLA antibodies, the sex difference, and the normal PHA and MLC response before grafting. After the graft, the disappearance of anti-HLA antibodies has a good prognostic value. The appearance of autolymphocytotoxins seems to correlate strongly either with rejection or graft-versus-host disease.

The indications and results of allogeneic bone marrow transplantation are well known by the analyses of European and International registries. In acute nonlymphoblastic leukemia in first CR, the disease-free survival (DFS) is 45% with a risk of relapse (RR) of 15%, in ALL in first CR the DFS is 60% with a RR of 15%, in ALL in second CR the DFS is 40% with a RR of 30%, and in CML in the chronic phase the DFS is 60%, with a RR of 20%. These results must be adjusted with other risk factors such as age, sex mismatch, disease status, CMV serology, and GvHD. The use of donors who differ from genotypically matched related donors is currently under investigation. Mismatched related transplants give disappointing results except in the case of 1 HLA mismatch. Unrelated HLA-matched donor panels have recently been established in various countries with 200 transplants performed with a DFS of approximately 40%. Researchers are currently trying to reduce the RR by intensifying the conditioning regimen or using the graft-versus-leukemia effect of allogeneic T cells, reducing GvHD by the use of monoclonal antibodies, and improving the engraftment by the use of growth factors. The recent use of cryopreserved cord blood cells for transplantation may improve the results of partially mismatched transplants in children.

An ultrastructural study was performed on skin biopsies of eight patients with lichenoid eruption of chronic graft-versus-host disease (GVHD). The lichenoid eruption is similar to idiopathic lichen planus with the injury of the basal cells, the distribution of the numerous colloid bodies, and the presence of regenerative cells. Lymphocytes satellites of injured keratinocytes were observed in those lichenoid eruptions, as well as in the acute phase of GVHD. The numerous mast cells in the lichenoid eruption of GVHD may be related to the connective tissue changes of the patients progressing to a late sclerotic phase of chronic GVHD.

This articles summarizes the experience of the Hospital Saint-Louis Bone Marrow Transplantation Team of bone marrow transplantation in severe aplastic anemia. Sixty-five consecutive patients have been transplanted with an HLA identical sibling marrow. Various conditioning regimen have been used. Conditioning regimen using high dose Cyclophosphamide alone or associated with Procarbazine and anti-thymocyte globulin gave a high number of bone marrow graft rejection. Therefore, a conditioning regimen using Cyclophosphamide and total body irradiation with lung shielding has been used for the last three years. This regimen suppressed bone marrow graft rejection. The main problems remain graft versus host disease and intercurrent infections. Despite these complications, 50 per cent of the patients become long term survivors and are apparently cured of their initial disease.

The SAA Registry of the EBMT now contains data on 171 children younger than 15 years of age with acquired SAA and undergoing BMT between 1970 and 1988. The overall actuarial survival is 63% at 10 years. In a multivariate Cox analysis, the year of transplant was the most important prognostic factor with a significant advantage for children grafted in 1984-88 (81%) vs 1981-83 (67%) and 1970-80 (41%) (p = 0.02). Cyclosporine A given for GVHD prophylaxis, no treatment before transplant and an interval less than 90 days from diagnosis to BMT were all favourable variables in univariate analysis. As regard to transplant procedures, the better results were obtained using Cyclophosphamide and Cyclosporine A (78%) followed by Cyclophosphamide plus irradiation plus Cyclosporine A (77%). Sex, etiology and the severity of the aplasia had no impact on survival in both uni and multivariate analysis.

Various opportunistic infections have been described in patients treated with allogeneic bone marrow transplantation (BMT). Acute disease with toxoplasma gondii is a significant cause of mortality and morbidity in transplant patients. The difficulty of diagnosis and the possibility of an effective treatment in case of early diagnosis prompted us to prospectively perform serial serological studies in BMT donors and recipients, in order to correlate the evolution of antibody titers and the clinical evidence of toxoplasmosis. We studied 80 consecutive patients. Antibody titers were measured before transplant in donors and recipient’s sera. After transplant, they were measured every two weeks for 3 months and then every 3 months. All patients described here have been followed for a least 3 months. Both indirect immunofluorescence antibody test and direct agglutination test were performed on each sample.

By means of indirect immunofluorescence with human sera it has been demonstrated that cytoplasmic components of the basal cell layer showed antigenic differences as compared to the upper cell layers. Moreover there were differences whether the cells were involved in a mucous, a parakeratinized or an orthokeratinized differentiation.

The etiology of aplastic anemia is unknown. A stem cell lesion caused by a toxic or a virus or a microenvironment defect are the main hypothesis. An auto-immune origin has been recently suspected but never proved. To demonstrate the auto-immune origin of the disease. We have treated 17 patients with severe aplastic anemia with antilymphocyte serum (ALS). Nine patients showed no improvement and seven patients died within two months of infectious or hemorrhagic complications. In contrast, eight patients had a prompt rise of granulocytes and reticulocytes counts. Although the hematological reconstitution is not complete. This eight patients are still alive between 4 months and 15 months after treatment. This study shows that A.L.G. may have a beneficial effect in the treatment of patients with severe aplastic anemia.

Four patients developed legionnaires' disease after bone marrow transplantation. Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply. The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge. The outcome was good in two patients. In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin. The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin. During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination. The fourth patient in this report was receiving no antibiotics. Thus pefloxacin seems to be effective as prophylaxis against L. pneumophila infection. When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared.

The prevalence of AIDS now approaches 1% in patients with hemophilia and laboratory evidence of abnormal immunoregulation is found in 50% of patients with severe hemophilia. Current evidence indicates that a human retrovirus HIV/LAV is the etiologic agent which can be transmitted through the administration of blood products. We reported 7 cases in childhood, 5 acute leukemia, 1 metastatic neuroblastoma, and 1 severe aplastic anemia in whom AIDS occurred after administration of blood products. To date 5 patients are alive and 2 have died of infections. It is suggested that the use of steroids or antineoplastic agents increases the incidence of AIDS in patients infected with HIV/LAV because of altered immune suppression. The maintenance treatment is difficult in these patients. The widespread use of HIV serology to screen donated blood should help to prevent AIDS transmission in leukemic patients.

The state of cellular alloimmunity in haemodialyzed patients has been assessed by a microcytotoxicity assay and compared with that in healthy donors. Some of the patients were also studied during the weeks following a first kidney transplant rejection. For comparison, lymphocytes of multiparous women have been studied. Skin fibroblasts from a panel of normal donors were used as targets, and effector cells were cryopreserved peripheral blood lymphocytes. Lymphocyte-mediated cytotoxicity (LMC) demonstrated restricted reactivity against target cells, an indication of specificity. It detected presensitization more often than a standard test for cytotoxic antibodies. This difference is not attributable to differences in sensitivity of the two tests, since some patients were at least once LMC negative and cytotoxic antibody positive, and the antigens detected by both tests were different in patients who had positive LMC and cytotoxic antibodies simultaneously. In some experiments, LMC target determinants were not HLA serologically detectable antigens. Furthermore, lymphocytes obtained after transplant rejection were cytotoxic for targets which did not share the donors' serological mismatches. These results suggest that antigens other than HLA-A and B may be the determinants recognized in the microcytotoxicity assay.

CMV infection is one of the major infection after bone marrow transplantation. CMV viremia was systematically studied in 66 patients with aplastic anemia or leukemia undergoing BMT. 57% patients had CMV viremia with a frequency peak between 7 and 9 weeks after transplant. Clinical symptoms found during viremia were pancytopenia, fever, cytolytic hepatitis. Interstitial pneumonitis was found only in 4 cases. In 3 cases, viremia was not associated with clinical symptoms. Survival was identical to the group of patients without viremia. Viremia was positively associated with the presence of high anti-CMV antibody titer in donor or recipient before transplant, or to a lymphocyte proliferative response against CMV antigens in donor or recipient before BMT. Granulocyte transfusions increased the frequency of CMV viremia. CMV infection was significantly associated with acute and chronic graft versus host disease. The relation showed between these parameters and viremia provides a basis for an accurate diagnosis of CMV infection and a better background for the study of prophylactic or curative treatment of CMV infection.

In a series of 198 patients we compared various methods of prevention of GVHD. One hundred and thirty-three patients were treated with CSA alone, 44 with the combination of CSA and MTX, and 21 with CSA after marrow T cell depletion. The incidence of GVHD greater than or equal to II was 35% in the CSA group, 22% in the CSA+MTX group and 14% in the T depleted group. The actuarial survival was 55.4%, 52.3% and 55.1% respectively. These results show that the improvement of methods of prevention of GVHD did not affect significantly long term survival after BMT.

The case of a 42 years old man who had a monoblastic acute leukemia treated by a bone-marrow graft is described. The patient died of a cerebral toxoplasmosis and a cerebral computed tomography done two days before is correlated with anatomopathologic slices done in the same planes than the computed tomagraphy examination. There is a good correlation between necrotic abceded areas and hypodense areas accompanied by serpiginous fixations of contrast media. The immunocompromised patient is very favorable for the development of a cerebral toxoplasmosis. CT, while not specific, has the advantage to suspect the diagnosis which must be discussed with other oportunistic infections, leukemic infiltrates, methotrexate encephalopathy, progressive multifocal encephalopathy, and small infarcts.

Between August 1979 and April 1986, we treated 70 patients with chronic myeloid leukemia by supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) from HLA identical sibling donors (65 patients) or from identical twins (5 patients). All patients were splenectomized before BMT. To prevent graft versus host disease Cyclosporin alone or associated with Methotrexate was given; in addition 13 patients received a T cell depleted marrow. All patients showed engraftment. Of the 5 patients treated by syngenic BMT, 2 patients relapsed but all are alive in remission, 2 of them after a successful second BMT. Of the 36 patients treated by allogeneic BMT in the chronic phase, 20 are alive in unmaintained remission after a median follow-up of 24 months (range 6 to 58). No patients have relapsed. The actuarial survival at 2 years was 60%. Of the 29 patients with more advanced disease, 19 have survived with the actuarial survival at 2 years 50%. We conclude that the probability of cure after BMT is very high, especially if BMT is performed while the patient remains in the chronic phase. Only 3 patients grafted in accelerated or blast phase died with relapse. The main cause of death was interstitial pneumonitis (15 patients) and 10 patients died from other transplant-related complications.

In immunosuppressed patients (pts), cytomegalovirus (CMV) viremia is an accurate marker for disseminated CMV infection as opposed to urine excretion or changes in antibody titers. A systematic study of CMV viremia was serially performed after allogenic transplantation (BMT) in 96 pts whose the clinical manifestations related to viremia were described. The occurrence of viremia was examined according to graft versus host disease (GVHD) and pts or donor pretransplant immunity against CMV.

In 68 idiopathic aplastic anemia patients (65 HLA genotypes), HLA-A2 is slightly increased (p corrected less than 0.03) leading to a relative risk of 2.30. A slight excess of homozygotes for HLA-A was observed (22.2 vs. 14.09%), involving mostly the A2 antigen. In the siblings the patients were more frequently homozygote A2 than by chance (p less than 0.005). The same trends are observed in Fanconi's anemia = out of 18 patients, 7 are HLA-A homozygote (of whom 4 are A2). The hypothesis of the existence of one or several recessive genes involved in hematopoiesis situated close to HLA-A is advanced.

Skin is a target organ for Graft v Host Reaction (GvHR). Cutaneous changes sometimes are the first symptoms for GvHR. They offer the opportunity for its early recognition. They include: -- A primarily acute phase, as red maculopapular rash, on face, palms and soles, which can spread over large areas, resembling scarlatiniform rash. Some courses have resulted in severe epidermal necrolysis similar to Lyell syndrome. -- A chronic phase, described with a variable time of onset after the acute episode. Two stages have been recognised: -- the early chronic phase has a clinical and histological picture similar to Lichen Planus, a frequent dermatosis which is thought to be the result of a chronic immune injury against epidermis. As early phase is fading, an atrophic aspect of the skin may develop, whose severe type is described as Poïkiloderma. -- The late chronic phase, in which densification of dermal collagen is become the essential features. In some patients, sclerotic changes develop, which are resembling to scleroderma ones. The cutaneous manifestations of GvH Disease can be responsible for considerable morbidity, mortality and sequelles. They may serve as a biological model for several skin diseases.

Chronic graft-versus-host disease (GVHD) is a very heterogeneous entity with variable clinical expression. The pathophysiology involves autoimmune disorders and features of fibrosis. Four patients transplanted for severe aplastic anaemia conditioned with cyclophosphamide and thoraco-abdominal irradiation developed skin scleroderma specifically localized in the irradiation fields. This syndrome was remarkable for its late onset and the absence of factors known to trigger chronic GVHD. It is postulated that irradiation used in this protocol may induce keratinocyte damage and trigger chronic GVHD.

Forty-one patients, suffering from severe aplastic anaemia were treated either with ALG alone (27 patients) or ALG followed by infusion of allogeneic bone marrow (14 patients). Eighteen patients (67 per cent) are presently alive after ALG alone at over 100 to over 550 days. Fourteen (52 per cent) showed sustained improvement of haematopoiesis, two are alive without change, one recovered autologous haematopoiesis after cyclophosphamide conditioning and transfusion of HLA identical marrow and one is lost to follow-up. Eight patients (57 per cent) are currently alive after ALG and transfusion of haplotype identical marrow with self-sustaining autologous haematopoiesis at over 200 days to over four and a half years. No lethal complications occurred and none of the bone marrow infusions led to permanent engraftment or graft-versus-host disease. The mechanism of action is not known, but our results support the hypothesis that unspecified autoimmune reactions block the normal outgrowth of haematopoietic precursor cells in a substantial number of patients with aplastic anaemia. This therapeutic approach seems to offer good chances of survival, especially for those patients who do not have an HLA identical sibling. Its value should be further investigated.

Chronic granulocytic leukemia (CGL), characterized by the Philadelphia chromosomal abnormality [1], is a clonal [2] myeloproliferative disorder with poor prognosis [3]. The main cause of death is blast crisis, which is often preceded by an accelerated phase. Blast crisis is generally refractory to chemotherapy and fatal within a few months. Conventional chemotherapy can improve the quality of life during the chronic phase but cannot delay the onset of blast crisis. Aggressive chemotherapy during the chronic phase gives poor results because cytogenetic conversions are uncommon, incomplete, and usually transient. Expectations that autografting would prolong survival for patients in blast crisis have not been confirmed. Because of these disappointing results, several investigators began to evaluate supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) as a potential therapeutic modality [4–8]. We report here the results of a retrospective analysis of 160 patients who received transplants between 1981 and 1985 in 18 French centers.

Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in 16 of 27 patients with transient initial engraftment but in none of ten patients with no sign of engraftment after the first transplant. The major factors associated with a reduced risk of graft failure were use of radiation for pretransplant immunosuppression and use of cyclosporine rather than methotrexate or T- cell depletion of the donor bone marrow for prophylaxis against graft-v- host disease (GVHD). Among 266 patients prepared for transplantation with cyclophosphamide alone, the risk of graft failure was increased in patients who received previous transfusions and reduced in those who received corticosteroids for previous therapy. Neither cell dose nor administration of donor buffy coat cells affected the probability of engraftment. Although use of radiation in conditioning reduced graft failure, survival was not improved. Posttransplant treatment with cyclosporine and avoidance of pretransplant blood transfusions were associated with improved survival.

In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.

A program to obtain volunteer bone marrow donors has been developed. A total of 33.000 HLA-A, B typings were performed. A search for 527 patients has been initiated. Among these, 44% are suffering from chronic myelogenous leukemia. For 23% of the patients no HLA-A, B identical donor has been identified. Out of the 401 patients who had HLA-A, B identical donor 35% (139/401) had one or more HLA-A, B, DR identical donors. In one of the transplant center, when the mixed lymphocyte culture (MLR) was carried out between 219 donors and 79 patients, a transplantation for 20/79 patients has been proposed. Up to now, transplantation has been carried out in 31 patients whom donor searches were initiated.