Successful bone marrow transplant for Fanconi's anaemia.

A 15-year-old boy with Fanconi''s anaemia, who required four units of blood each month, received a bone marrow graft from his 9-year-old brother, who has HLA identical and compatible on mixed lymphocyte reaction. Considerable immunosuppression was used and bacterial infection was prevented by vigorous decontamination in a Vickers-Trexler isolator. After the graft the patient''s blood counts remained satisfactory for nine months, but it took six months before qualitative immune function was normal.     

No narcosis for bone marrow harvest in autologous bone marrow transplantation

A prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation. This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.     

New stains for blood and bone marrow cells.

Traditionally, blood and bone marrow cells have been identified based on their characteristic shapes and colors when stained with one of several panoptic stains including Wright's or Giemsa's. As questions arose regarding the origin of normal and leukemic cells, cytochemical stains were developed. These stains help identify cells on the basis of a distinctive metabolite or enzyme. As part of an ongoing tradition in which textile dyes are used for biological staining, several new stains have been applied to hematologic staining. These include C.I. basic blue 41, basic blue 141, basic blue 93, and an asymmetrical polymethine dye. As additional cell-selective stains are developed, we can anticipate further improvements in our ability to identify normal and malignant hematopoietic cells.     

Antioxidants for bone marrow cryopreservation

Addition of antioxidants into the preservation solution improved the cryoprotection of human bone marrow cells. The viability was studied by the growth of GM-CFC in agar culture before and after storage at -196 degrees C. All used antioxidative drugs (selenomethionine, methionine, tocopherol, penicillin/Fe++) increased the tolerance of the stem cells to freezing and thawing and elevated the number of surviving GM-CFC up to the twofold in comparison with that of controls. More immature colony forming cells were especially protected.     

Comparison of bone marrow extracellular matrices.

We have compared the structure and composition of adult and fetal bovine bone marrow extracellular matrices. In contrast to fetal bone marrow, adult bone marrow has more oval fenestration and accumulation of adipocytes as well as lower protein content. These differences could be due to remodeling of bone marrow tissue as it develops. Zymogram analysis of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) activities showed that fetal, but not adult bone marrow extract contained a 96-kDa MMP and TIMP-1 and -2. These activities may contribute to the structural differences between adult and fetal bone marrow tissues.     

Registry of unrelated bone marrow donors.

Reports of successful transplantation of bone marrow obtained from unrelated donors who were histocompatibility leukocyte antigen (HLA) identical prompted the Canadian Red Cross Blood Transfusion Service in Ottawa to assess the possibility of developing a bone marrow donor registry in Canada. We sent a pamphlet that explained the program to 1568 people who had undergone apheresis and asked them to reply, stating their interest. At the same time the pamphlets and a poster were placed in the blood donor clinic. We received 1232 replies (78.6%) from the apheresis donors, 838 (68.0%) of which indicated a willingness to attend information sessions. Of the 7158 people who gave blood during the 3-month study period, 225 (3.1%) were interested. At the time this paper was written 47 information sessions had been held, and 721 people had attended, 624 (86.5%) of whom had signed a consent form. This indicates a clear interest in a bone marrow donation program. We believe that the ethical issues are overcome by requesting the donation before identification of any patient. From our experience a national registry of unrelated donors seems feasible, and steps are being taken to implement such a program.     

The immunoregulatory role of bone marrow. IV. Role of an immunoenhancing glycoprotein derived from murine bone marrow

Bone marrow-enhancing factor (B-EF) is the spontaneous product of whole bone marrow cells cultured in serum-free medium for a short term (24-48 hr). The factor is prepared by ultrafiltration of BMC supernates to yield a preparation with a MW of greater than 10,000. Production of the factor is not dependent upon antigenic or mitogenic stimulation of BMC, but is inhibited by treatment of BMC with cycloheximide. B-EF augments the in vitro primary PFC response to SRBC, as well as in vitro secondary IgM and IgG PFC responses to SRBC. Enhancement by B-EF is antigen dependent, genetically nonrestricted, and maximal when present at the initiation of culture. B-EF cannot induce a polyclonal antibody response like the polyclonal activator LPS. B-EF is directly mitogenic for thymocytes, bone marrow, and whole spleen cells, but fails to act as a costimulator of thymocyte proliferation in the presence of Con A. B-EF cannot support the growth of the IL-2-dependent cell line CTLL-2. Since B-EF has not been purified, the supernatant may contain more than one activity. The factor is heat labile at 65 degrees C and is sensitive to enzymatic digestion with trypsin and neuraminidase; this implies that B-EF may be a glycoprotein.     

An overview of bone marrow transplantation for chronic myeloid leukemia.

The use of intensive therapy together with transplantation of marrow from a suitable donor is the only established curative treatment for patients with chronic myeloid leukemia (CML). However, marrow transplantation is hazardous, costly and applicable to relatively few patients. Therefore, we evaluated the results and limitations of marrow transplantation for CML and discussed new treatment strategies. We decided to select a limited number of papers that focused on the relevant issues rather than to undertake an exhaustive comparison of treatment results from different centres. Patients with CML in the chronic phase who receive marrow from a sibling with the same human leukocyte antigen type can expect to have a long-term disease-free survival rate of 50%. However, the procedure is associated with a mortality rate of 30%, mainly because of graft-versus-host disease (GVHD) and interstitial pneumonitis. Moreover, because of the requirements for age and histocompatibility only 10% of patients with chronic-phase CML are currently eligible. Transplantation earlier in the chronic phase (within 1 year after diagnosis), the use of marrow from matched, unrelated donors and the development of improved methods for reducing the incidence of GVHD all hold promise. In addition, the preliminary results of intensive therapy followed by transplantation with cultured autologous marrow have been encouraging. If further progress is to be made, continued optimism coupled with carefully developed and executed studies will be necessary.