Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Negligible clinical effects of thalidomide in patients with myelofibrosis with myeloid metaplasia.

We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with myelofibrosis with myeloid metaplasia (MMM), with or without preceding polycythemia vera or essential thrombocythemia, with a primary aim to improve anemia. Thalidomide was given in escalating doses with a target dose of 800 mg daily, but the median dose of thalidomide that was actually tolerated was 400 mg daily. Fifteen patients were entered into the study and 14 were evaluable for response. Five of 14 (36%) patients discontinued thalidomide before 3 mo because of side effects, and none of these five patients had a response at the time when thalidomide was stopped. When evaluated after 3 mo of therapy, none of the remaining nine patients exhibited a discernible clinical response. Three patients showed progressive disease defined as > 50% increase in the need for red cell transfusions. Treatment was poorly tolerated, with all patients reporting side effects of thalidomide, the most prominent being fatigue documented in 80% of patients. Two patients died while on study, one from acute myelogenous leukemia and one from pneumonia. We conclude that thalidomide given in doses employed in the treatment of multiple myeloma gives no clinically relevant hematological effects in advanced MMM and is hampered by a very high incidence of side effects.

[A patient who recovered successfully from severe anemia which continued for one hour].

A 79-year-old woman had her cervical spinal cord injured and laminoplasty of the neck was performed. Uncontrollable venous bleeding was encountered during the operation and about 5000 ml of blood was lost in one hour. Massive infusion of 5% albumin and hydroxyethylstarch (HES) was done to maintain the intravascular volume. Therefore, her hematocrit value (Ht) decreased to 4.5%. Her rectal temperature went down to 34.5 degrees C. The operation was finished in haste. We studied leg pain experienced under spinal anesthesia in leprosy patients. Seven of twenty patients complained of the leg pain a few minutes after spinal block. The pain was localized in the parts of deafferentation or phantom limb, and was relatively mild and controllable. We consider that the inhibitory system is inactivated when the somatic impulse is blocked by spinal anesthesia, and as a result the abnormal burst activity of dorsal horn produced by peripheral nerve damage of leprosy causes phantom pain.

The prevalence of human T-cell leukemia virus type I infection in patients with hematologic and nonhematologic diseases in an adult T-cell leukemia-endemic area of Japan.

In order to clarify the prevalence of human T-cell leukemia virus type I (HTLV-I) infection in the Kagoshima district, Japan, a highly endemic area for HTLV-I, antibodies for HTLV-I (anti-HTLV-I) were examined in the sera of 6167 from healthy residents and patients with various hematologic and nonhematologic diseases. In healthy residents, including blood donors, the prevalence of anti-HTLV-I was 11.9% (562/4741 persons). The prevalence increased with age, and was significantly higher in in females than in males (P less than 0.01). The prevalence of anti-HTLV-I in blood donors was 8.5%. In In hematologic diseases, the prevalence of anti-HTLV-I was 98.3% in ATL, 28.9% in lymphoproliferative disorders except ATL, and 10.6% in myeloproliferative disorders. In nonhematologic diseases, the prevalence of anti-HTLV-I was shown to be 29.5% in pulmonary tuberculosis, 25.8% in leprosy, 33.8% in chronic renal failure (CRF), 21.9% in autoimmune diseases, and 47.8% in strongyloidiasis. The various diseases except myeloproliferative disorders had significantly higher prevalence of anti-HTLV-I than healthy residents (P less than 0.01 or 0.05). For autoimmune diseases, the prevalence of anti-HTLV-I in patients with blood transfusion (55.6%) was higher than in those without blood transfusion (8.7%), and healthy residents. In hemodialysis patients with CRF who had received blood transfusions the prevalence of anti-HTLV-I increased with the number of blood transfusions. Therefore, HTLV-I transmission via blood transfusion would partially explain these high prevalence of anti-HTLV-I. However, the prevalence of anti-HTLV-I in hemodialysis patients with CRF was statistically higher than that in healthy residents, regardless of blood transfusion (P less than 0.01). Furthermore, hemodialysis patients showed significantly higher prevalence of anti-HTLV-I than healthy residents, even at a younger age. Patients with pulmonary tuberculosis and leprosy showed the same results as hemodialysis patients. These results suggest that possibility that HTLV-I infection has some relation not only to ATL but also to other diseases. Therefore, it seems very important to halt the spread of HTLV-I transmission as soon as possible.

Treatment of leprosy with weekly intravenous infusion of leukocytes.

Two patients with lepromatous leprosy were treated with weekly intra-venous infusions of leukocyte concentrates for a period of 12 consecutive weeks. A reversal reaction was induced in one of the patients, and it was possible to control chronic erythema nodosum leprosum in the other subject. Possible pathogenetic mechanisms involved in the induction of these changes include the action of transfer factor, interactions between B- and T-lymphocytes or the mediation of a lymphokine necessary for the effective function of the cell-mediated immunity. Immunotherapy for chronic infections, such as leprosy, still has not become a reality.

Reversion of the downhill course of active lepromatous leprosy by repeated transfusions of fresh blood, donated by healthy but lepromin positive patients.

Earlier studies of immunologic reconstitution therapy of active lepromatous leprosy patients by repeated infusions of viable allogeneic blood lymphocytes indicated a beneficial effect. In order to avoid cell separation and its associated risks, we attempted to transfer immunity passively into seven seriously ill lepromatous patients by repeated transfusions of fresh blood donated by healthy, but tuberculin and lepromin positive, subjects. The results showed clinical improvement in some cases with the elimination of Mycobacterium leprae, histological reversion and return of immunologic responsiveness.

An attempt at passive transfer of immunity to leprosy patients by transfusion of allogeneic lymphocytes, inactivated with mitomycin C.

An attempt was made to repair cell-mediated immunity in 7 patients suffering from lepromatous leprosy and severe erythema nodosum leprosum by intravenous infusion of 400 million allogeneic blood lymphocytes on 3 occasions. The lymphocytes were obtained from lepromin and tuberculin-positive subjects and were inactivated in vitro by treatment with mitomycin C. Immunotherapy with inactivated lymphocytes only modified the severity of erythema nodosum leprosum, without altering other aspects of the disease.

Passive transfer of immunity into leprosy patients by transfusion of lymphocytes and by transfusion of Lawrence's transfer factor.

About 1,200 million viable lymphocytes from normal but lepromin- and tuberculin-positive human beings were transfused in four patients of lepromatous and one of tuberculoid leprosy three times at monthly intervals. Three patients of lepromatous leprosy suffered from erythema modosum, whereas the other two developed severe reaction whenever put on the smallest dose of dapsone. In one patient of lepromatous leprosy, minimal improvement or none was observed, whereas in the remaining three cases of lepromatous and one of tuberculoid leprosy, clinical, bacteriological, as well as histological improvement occurred. Two of the five patients started to tolerate the dapsone during the period of study. The present study indicates that immunotherapy might have a definite role in the management of the disease especially in cases with erythema nodosum. Lawrence factor, prepared from leucocytes of normal donors, was transfused three times into four lepromatous leprosy patients who were intolerant to anti-leprosy drugs. The donors were healthy but were tuberculin and lepromin (Mitsuda) positive. The clinical, histological, bacteriological (morphological index), and immunological assessments of the patients were performed before and 5 months after starting the immunotherapy. In two patients conversion of Mitsuda reaction occurred, but there was no appreciable improvement in the clinical, histologic, and bacteriologic status of these patients.

Immunodeficiency in leprosy.

It is known that the impairment of cell-mediated immunity (CM) exists in lepromatous leprosy patients. This was shown by 1) delayed skin reaction to various test antigens, 2) decreased transformation of lymphocytes by various antigens, 3) delayed rejection of skin allograft, 4) decreased migration inhibitory fa-tor (MIF) formation, and 5) histologic study of the lymph node. In addition to these previous works, we have studied T and B lymphocytes in peripheral blood of leprosy patients; T cells by the technic of rosette formation, and B cells by staining surface immunoglobulins. The result of our study shows decreased numbers of T cells and increased numbers of B cells in peripheral blood of lepromatous patients. A the same time, we found that allogenic leukocyte infusion treatment reversed T and B-cell abnormalities. We know that repeated infusions of allogenic leukocytes dramatically brought about improvement of the clinical status of the patients, resolution of skin lesions, subsidence of erythema nodosum leprosum reaction, clearance of bacteria from the skin and lymph nodes, and reconstitution of peripheral lymph nodes.