[Acquired hemoglobin H disease in the early stage of erythroleukemia]. / Erworbene Hämoglobin H-Krankheit im Frühstadium einer Erythroleukämie.

At the onset of erythroleukemia, the patient, a 74-year-old Swiss male, was also found to have microcytic-hypochromic anemia (Hb: 82 g/l, MCV: 69 fl, MCH: 21 pg). Further laboratory examinations revealed reduced hemoglobin stability, a hemoglobin H fraction of 3.0% on cellulose acetate-electrophoresis, and an abundance of hemoglobin H inclusion bodies in red cells. These findings, as well as the Swiss origin of the patient and his age at the onset of the disease, were consistent with acquired hemoglobin H disease. In addition to genetic hemoglobin H disease, acquired hemoglobin H disease was reported to be associated with myelodysplastic and myeloproliferative syndrome, or erythroleukemia and acute myelogenous leukemia. The literature contains fewer than 50 cases. It is suggested that the molecular basis of this rare disease involves a gene in trans to the alpha-globin genes reducing the expression of all four alpha-globin genes to approximately 10% of normal activity.

Autologous bone marrow transplantation in the treatment of children and adolescents with advanced malignant tumors.

Nineteen patients with advanced malignant tumors, less than 20 years old were treated with intensive chemotherapy (vincristine 2 mg/m2 i.v. and adriamycin 60 mg/m2 i.v. on day - 7; cyclophosphamide 45 mg/kg i.v. on days -6 to -3), total body irradiation (TBI, 600 rads on day -1) and autologous bone marrow transplantation (ABMT, day 0). Prior to this procedure induction of complete or partial remission by conventional therapy was attempted. Ten patients had intra-abdominal non-Hodgkin's lymphoma (NHL); three, yolk sac tumor; three, Ewing's sarcoma; and three, neuroblastoma. The supportive care included reverse isolation, immunoglobulin 400 mg/kg i.v. q 2 weeks, cotrimoxazole per os, and cell support as needed. No correlation between the bone marrow dose and the time of hematological reconstitution could be established. Five of seven patients with intra-abdominal NHL stage III (transplanted in first remission) are surviving disease-free for 5+, 5+, 20+, 23+, and 35+ months after ABMT. None of three patients with intra-abdominal NHL stage IV is surviving (two of them were transplanted in second remission). One of three patients with yolk sac tumor is surviving disease-free for 27+ months. There are no survivors among the patients with Ewing's sarcoma and neuroblastoma. Only one of 19 patients was lost due to therapeutic complications, while 12 died due to tumor. Regarding treatment results for advanced intra-abdominal NHL, the procedure described here is comparable to the best conventional regimens. In vitro methods for tumor cell eradication in the collected bone marrow might further improve the results of ABMT.

Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia.

A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly anti-HLA) occurred less frequently (p less than 0.002), after a longer time period (p less than 0.002), and after a higher number of transfusions (p less than 0.005) as compared to MD patients. SD patients also became refractory to random platelets less frequently (p less than 0.005), after a longer time period, and after a higher number of transfusions (p less than 0.02). In SD patients, the increments after the first and the last transfusion were in the same range, whereas in MD patients, the 1-hr (p less than 0.001) and the 24-hr (p less than 0.025) increments decreased from the first to the last transfusion. Thus, the use of random SD platelet transfusions postponed alloimmunization.

Influence of the spleen on the distribution of blood neutrophils. Quantitative studies in the rat.

The influence of the spleen on the distribution of blood neutrophils was studied in rats with varying spleen sizes following transfusion of isologous 3H-dT-labelled neutrophils. The weight of the spleen correlated with the splenic neutrophil pool (r = 0.87, P less than 0.01). Alterations in spleen size did not significantly change the total blood neutrophil pool, but with increasing splenomegaly circulating and marginal neutrophils were shifted into the splenic pool. With massive splenomegaly, up to 50% of the total blood neutrophils were trapped in the spleen. These findings suggest splenic pooling of neutrophils and a shift of circulating and marginal neutrophils into the spleen proportionate to the splenic tissue present.

[The 5q syndrome--a chromosome aberration with characteristic hematologic picture: preleukemia? Literature review and description of a personal case]. / Das 5q-Minus-Syndrom--eine Chromosomenaberration mit charakteristischem hämatologischen Bild: Präleukämie? Literaturübersicht und Beschreibung einer eigenen Beobachtung.

The case of a 74-year-old woman with macrocytic, refractory anemia, typical changes in the bone marrow and a 5q-chromosome in bone marrow cells is presented and the literature of this newly described hematological disorder is reviewed. The syndrome is characterized by partial deletion of the long arms of a chromosome No. 5 in bone marrow cells. The chromosomal anomaly is acquired and originates most probably from a pluripotent hematologic stem cell. Hematologic changes are (1) macrocytic, refractory anemia, (2) low to normal leukocyte counts, (3) normal to increased platelet number with marked anisocytosis and a high proportion of megathrombocytes, (4) normal to hypoplastic erythropoiesis and generally small megakaryocytes with nonlobulated nuclei in the bone marrow. In most of the reported cases (16 out of 19) with isolated 5q-anomaly, the clinical picture and laboratory findings remained stationary during a follow-up period of up to 6 years. In only 2 out of 19 cases did acute leukemia develop. In the presence of additional chromosomal abnormalities, all the cases developed acute leukemia and especially acute myelogenous leukemia. The diagnosis of 5q-syndrome in patients with refractory anemia is of prognostic significance, since it renders possible early recognition of a potentially malignant disorder and early detection of leukemic transformation.

Isolation of granulocytes and labelling with indium 111-oxine sulphate.

The isolation of granulocytes from whole blood and labelling with Indium 111-oxine sulphate are described in detail. To isolate the cells a two-step method was used: (1) removal of the red blood cells by methyl cellulose-Ronpacon and (2) separation of the leucocyte-rich plasma with a double gradient (1077, 1097) technique. 111In-oxine sulphate was prepared by adding 111In-chloride to a buffered solution of oxine sulphate. The labelling of the granulocytes with 111In-oxine sulphate was done by incubation at room temperature for 5 min.

[Selective aplasia of neutrophils: auto-immune origin]. / Aplasie sélective des granulocytes neutrophiles: origine auto-immune.

Autoimmunity is a recognized factor in pure red cell aplasia and in some cases of aplastic anemia, but not in agranulocytosis. The case reported here demonstrated that pure neutrophilic aplasia of autoimmune origin may exist in man. A 75-year-old male is described who presented with complete agranulocytosis and absence of neutrophilic precursors in the bone marrow without thrombocytopenia or anemia. After 6 weeks, remission was induced by immunosuppressive treatment and 22 months later the patient is doing well without therapy. The absence of known cases of agranulocytosis, a good response to immunosuppressive therapy, and the demonstrated fact that the patient's peripheral blood mononuclear cells inhibit the growth of granulocytic colonies of normal human marrow in vitro allow the conclusion that this patient had pure neutropenic aplasia, probably due to autoimmune phenomena.

[Autologous bone marrow reimplantation in children with advanced tumor. First experiences of feasibility]. / Autologe Knochenmark-Reimplantation bei Kindern mit fortgeschrittenem Tumor.

In three children with metastatic tumor uncontrollable by conventional chemo- and radiotherapy, bone marrow was obtained under general anesthesia and cryopreserved according to a carefully developed protocol. The autologous bone marrow cells were reinfused after intensive cytostatic therapy and total body irradiation (2 patients). After an aplastic phase of 7--14 days the peripheral blood leukocyte and thrombocyte count began to recover. The toxicity of the intensive treatment preceding the autologous bone marrow transfusion, and the autologous bone marrow cells themselves were well tolerated. The aplastic phase was easily controlled by the use of granulocytes, thrombocytes and erythrocytes. Except for fever and mucosal ulcerations observed during the phase of extreme leukopenia, the general condition of the patients during partial isolation lasting 26--34 days was astonishingly good. One child died 13 weeks after returning home due to a local relapse. The other two patients survived for 6 + and 11 + weeks and are in complete and partial remission respectively. A further evaluation of the clinical significance of autologous bone marrow reimplantations appears to be feasible in pediatric oncology.

Postmitotic marrow neutrophils and neutrophil mobilization in man: role of the spleen.

The relationship between postmitotic marrow neutrophils (PMMN) and neutrophil increment in blood after an intravenous dose of 3 mg hydrocortisone/kg was studied in patients with normal-sized spleens and compared with splenectomized and splenomegalic patients. PMMN were quantified from the ferrokinetic measurement of the normoblast number and the PMMN/normoblast ratio in bone marrow biopsy sections. In 12 control patients with normal PMMN the increment was 3.50 +/- 1.13 X 10(9) neutrophils/liter. An excellent correlation was found between the number of PMMN and the maximal neutrophil increment (y = 826x - 1021, r = 0.93, p less than 0.001) among 24 patients with normal spleen size and a wide range of marrow cellularity. Significantly higher responses were observed in 10 splenectomized patients (y = 872x + 1429, r = 0.92, p less than 0.001). The two regression lines were shown to be parallel, indicating a diminution of the response by 2.5 X 10(9) neutrophils/liter in the presence of a normal spleen. In 11 hypersplenic patients the responses were further reduced and more variable. Peak neutrophilia occurred after median values of 2, 3, and 4 hr in the hypersplenic, the control, and the splenectomized group, respectively. These studies indicate that allowing for the different response curves neutrophil increments may be used as an index of PMMN in patients with normal spleen size and in splenectomized patients. They further suggest sequestration of the prematurely released cells by the spleen.

Non-Hodgkin's lymphoma terminating in acute myelogenous leukemia.

The number of patients with non-Hodgkin's lymphoma who develop acute myelogenous leukemia is relatively small. The case of a patient with histologically proven diffuse histiocytic lymphoma who died with unequivocal acute myelogenous leukemia 5 years after the lymphoma diagnosis is presented. The difficulties in differential diagnosis are cited with a review of the literature.

[The effect of various cryoprotective agents on the human bone marrow]. / Einfluss verschiedener Gefrierschutzmittel auf menschliches Knochenmark.

The following combinations were evaluated as cryoprotectors of human CFU-c enriched bone marrow frozen for one hour at -190 degrees C: 10% DMSO, 1% DMSO + 9% dextran (Dx), 1% DMSO + 9% HES, 15% glycerin (Gc), 1% Gc + 9% Dx, 1% Gc+ 9% HES, 5% Gc + 4% glucose. Cell counts and CFU-c content were compared with controls left at 4 degrees C. Highest values were observed with 10% DMSO and with 1% DMSO + 9% Dx. These studies confirm the superiority of DMSO to Gc as a cryoprotector. With the combination of 1% DMSO + 9% Dx the removal of DMSO prior to reinfusion of the marrow is obviated. This should facilitate the clinical use of autologous marrow transfusion.

[Rise in neutrophils after hydrocortisone seen as bone marrow reserve mass. Dependency on spleen size]. / Neutrophilenanstieg nach Hydrocortison als Mass der Knochenmarkreserve. Abhängigkeit von der Milzgrösse

In 25 patients with a wide range of postmitotic marrow neutrophil mass a linear relationship was observed between the number of postmitotic marrow neutrophils and the rise of blood neutrophils after intravenous injection of 3 mg hydrocortisone/kg. Related to marrow neutrophil cellularity, the response curve was significantly higher in 10 splenectomized patients but greatly depressed in 10 patients with splenomegaly.