Jukka Nikoskelainen

Allogeneic bone marrow transplantation in multiple myeloma

Abstract Background and Methods. In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. Results. At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remi...

Allogeneic Bone Marrow Transplantation in Multiple Myeloma

Abstract Background and Methods. In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. Results. At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remi...

Viral Antibodies in the Sera from Patients with Parkinson Disease

An assay of antibodies to 15 various viruses and mycoplasma pneumoniae was performed on the serum specimens from 441 patients with Parkinson disease and from 443 healthy controls matched by sex, age, and place of residence, or from a representative group of these matched pairs. The main finding was a higher herpes simplex complement-fixing antibody level in patients with Parkinson disease than in controls. Patients with Parkinson disease had higher herpes simplex antibody titers more often than did their matched controls, and the matched controls, respectively, had low titers more often than the patients. The mean herpes simplex antibody titer (log2) of the patients (4.9) was significantly higher than that of controls (4.6) (p less than 0.01). This difference was also demonstrable when matched pairs were analysed for paired differences of herpes simplex antibody titers. For other viral CF and HI antibodies studied and for mycoplasma pneumoniae CF antibody, there were no significant differences either in the mean titers or in the distribution of individual titer values between the patients with Parkinson disease and the matched controls.

Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukaemia Working Party prospective analysis from HLA-typing.

Summary. The optimal post‐remission therapy for patients with acute myeloblastic leukaemia remains controversial. Allogeneic bone marrow transplantation, autologous bone marrow transplantation, and consolidation chemotherapy are the major options. In order to evaluate their respective value the European Group for Bone Marrow Transplantation conducted a prospective registration study. Patients with newly diagnosed acute myeloblastic leukaemia were registered at the time of HLA‐typing and intention to treat in case of presence or absence of an HLA‐identical donor was recorded. 27/79 (34%) patients HLA‐typed at diagnosis had an identical donor identified. The estimated survivals at 3 years from HLA‐typing were 44% and 21% among patients with or without HLA‐identical donor, respectively (P= 0·02). 22/26 (85%) patients for whom allogeneic bone marrow transplantation was intended were transplanted but only 15/47 (32%) patients for whom autologous bone marrow transplantation was intended were indeed transplanted (P < 0·001). The survival was 50%. 29% and 17% (P= 0·004) for patients treated with allogeneic bone marrow transplantation, autologous bone marrow transplantation, or chemotherapy, respectively. 40/68 patients HLA‐typed in first complete remission had an HLA‐identical donor. The estimated 3‐year survival among patients typed in first remission with and without HLA‐identical donors was 42% and 35% (n.s.), respectively. This technique of early patient registration illustrates the problems of patient selection during the course of the disease and might be used as a complement to randomized trials when comparing bone marrow transplantation and other treatment options.

A LONGITUDINAL STUDY ON ANTIBODIES to MEASLES and RUBELLA VIRUSES IN PATIENTS WITH MULTIPLE SCLEROSIS. A PRELIMINARY REPORT

Increased levels of antibodies to measles virus in serum specimens of patients with multiple sclerosis (MS) and local production of these antibodies in the central nervous system (CNS) of these patients have heen observed hy many research groups ( S a l m i 1973) . The implications of these ohservationb are unknown a t the present time. For instance, i t is not known whether there is any fluctuation in the production of measles antibodies in blS patients o r whether the antibody titers have any correlation with the clinical course of the disease in individual patients. It has heen suggested earlier that rubella virus might have some connection with MS (Salrni 1973) . The recent demonstration of some SSPE-like diseases having an evident rubella etiology fur ther supports the idea that ruhella virus could he one of the agents relevant to the etiology of hIS (TocunscJnd e t al. 1975) . In order t o collect information about the possible relationship hetween the disease coursc and virus antibody titers, a group of MS patients have been under close surveillance since 1970. The clinical course of the disease in this group of MS patients has been closely followed hy the Department of Neurology, Cniversity of Oulu, Finland. Serum and cerebrospinal f luid (CSF) specimens from the patients collected a t regular intervals are stored a t 40 C in the Department of Virology, University of Turku, Finland. The results of this report are based on studies of specimens collccted during the first 3 years of the surveillance period. The purpose of this work was to confirm and extend earlier reports on local antibody production against rubella virus in the CNS of some MS patients (Norrb!] e f al. 1974) and to describe the finding of relatively stable antibody ti ters to measles and ruhella viruses during the course of the MS disease.

VIRUS ANTIBODY LEVELS IN THE CEREBROSPINAL FLUID FROM PATIENTS WITH OPTIC NEURITIS

Virus antibody levels were studied in the cerebrospinal fluid (CSF) of 58 patients with optic neuritis and 58 control patients with no indication of multiple sclerosis (MS) or infectious disorders of the central nervous system (CNS). The specimens were tested against three different structural components of measles virus with measles hemagglutination inhibition (HI), measles hemolysis inhibition (HLI) and gel precipitation (GP) tests. Measles antibodies occurred in 62 per cent of CSF specimens from patients with optic neuritis, and 21 per cent of the controls. In the specimens from patients with optic neuritis, the positive rate figures were: for rubella HI test 35, parainfluenza‐1 HI 16, and Epstein‐Barr virus immunofuorescence (IF) 53 per cent. The frequencies in the control group were 10, 10 and 26 per cent, respectively. Serum/CSF antibody ratios below 80 occurred in measles tests in 45 per cent of patients with optic neuritis and 16 per cent of the control group. Some patients with optic neuritis (but none from the control group) had a reduced serum/CSF antibody ratio in more than one measles antibody test. The patients with optic neuritis had a higher frequency of low serum/CSF albumin ratios indicating blood brain barrier damage. There were, however, several patients with a normal serum/CSF albumin ratio but low serum/CSF immunoglobulin G and measles antibody ratios. This supports the hypothesis that local production of measles antibodies takes place in CNS in some patients with optic neuritis as well as in MS patients. The CSF specimens were further tested against 12 other viruses and mycoplasma pneumoniae complement fixation, but there were no positive specimens. New CSF specimens were taken from five patients during optic neuritis, and from seven patients later on during the follow‐up because of the appearance of new neurological symptoms. There were no changes in virus antibody levels, except for two patients with an increase of measles virus antibody titres.

Effect of cardiopulmonary resuscitation-induced stress on cell-mediated immunity

Functions of cell-mediated immunity were studied from 11 patients after cardiovascular resuscitation and from matched controls who were simultaneously under observation. The resuscitated patients were anergic to recall skin antigens (93% negative) as compared to the controls (62%) (p(0.01). The anergic state correlated with the outcome of the patients. Lymphocyte numbers did not differ between these groups, but the number of T cells was significantly decreased, and B cells and granulocytes was increased in resuscitated patients. Lymphocytes from resuscitated patients responded to mitogenic stimulation although the responses were lower than those of the controls. Decreased lymphocyte responses were partly due to serum factor(s) which were not attributable to serum cortisol concentration. In addition the findings favour a change in the compartmentalization of lymphocyte subsets resulting in increased number of suppressor cells and/or increased sensitivity of lymphocytes to suppressive humoral factor(s) in the circulation. The anergy in skin evidently represents the final outcome of the dysfunction of several arms of cell mediated immunity.

Graft‐versus‐leukaemia activity associated with cytomegalovirus seropositive bone marrow donors but separated from graft‐versus‐host disease in allograft recipients with AML

To elucidate whether a relationship existed between bone marrow donor cytomegalovirus (CMV) immune status and the probability of staying in remission after transplantation, a retrospective multicentre analysis was performed in 69 patients who received allogeneic bone marrow transplantation during relapse or second remission of AML or second remission of ALL. None of 12 AML patients with CMV seropositive donors had posttransplant relapse, in contrast to 7 of 10 AML patients with seronega‐tive donors. Kaplan‐Meier estimates of the 2‐yr probability of staying in remission for the two groups were 100% and 0%, respectively (p < 0.0005). This effect was independent of disease stage, donor and recipient age, recipient pretransplant CMV immune status and the occurrence of posttransplant CMV infection in recipients, and was not mediated through an increased occurrence of overt graft‐versus‐host disease (GvHD) in recipients with CMV seropositive donors. The increased probability of staying in remission was associated with an increased probability of 3‐yr disease‐free survival (p < 0.01). No similar effect was observed in patients with ALL. This study may suggest an allograft‐versus‐leukaemia effect in AML, associated with CMV seropositive donors, which seems separate from GvHD and independent of the occurrence of posttransplant CMV infection.

IS GROUP-SPECIFIC MENINGOCOCCAL VACCINATION RESULTING IN EPIDEMICS CAUSED BY OTHER GROUPS OF VIRULENT MENINGOCOCCI?

In 1976 routine vaccination against Neisseria meningitidis serogroups A and C was started in the Finnish Armed Forces. A case of fulminant, complicated pneumonia caused by group-Y meningococcus in a vaccinated recruit, prompted a study of the distribution of the meningococcal groups isolated from the recruits in the same unit. 14 (46%) of the 31 isolates from 84 recruits were group Y. Group-Y meningococcus was rarely isolated from unvaccinated controls. These results suggest that widespread vaccination against serogroups A and C may have led to an increase in the frequency of meningococcus group Y.

Virus antibody levels in serum specimens from patients with optic neuritis and from matched controls

Virus antibody levels in serum specimens taken in acute and convalescent phases from 77 patients with optic neuritis were tested by measles hemagglutination inhibition (HI), measles hemolysis inhibition (HLI), rubella HI, parainfluenza‐1 HI, Epstein‐Barr immuno‐fluorescence (IF), and against 11 other viruses and mycoplasma pneumoniae with the complement fixation (CF) technique. The virus antibody levels were indicated to be usually very stable, and a fourfold change in virus antibody levels was demonstrated in only eight patients. The virus antibody levels were compared with specimens from two carefully selected control groups. The first control group consisted of 71 healthy persons matched in age, sex and place of residence with the patients with optic neuritis. The other control group consisted of 58 patients with various neurological diseases other than multiple sclerosis (MS) or infectious diseases of the central nervous system. The patients with optic neuritis had significantly higher measles antibody titres than the two control groups in both measles HI and measles HLI tests. Also in 33 patients with optic neuritis of unknown cause, the measles antibody levels were higher than in the control groups. On the other hand, various other antibody tests showed no statistically significant differences between patients with optic neuritis and the control groups.