Showing papers in "American Journal of Hematology in 1986"

A serum ferritin assay for prevalence studies of iron deficiency

Abstract: A specialized serum ferritin assay has been developed for the detection of iron deficiency in epidemiologic studies. An enzyme immunoassay (EIA) was employed to eliminate the need for radioisotopes. The problem of low sensitivity inherent with the EIA for serum ferritin was eliminated by the use of monoclonal immunologic reagents. The working range of the assay is 1-100 micrograms/L with a sensitivity of 0.5 micrograms/L. Excellent agreement in serum ferritin levels was observed between the present method and the two-site immunoradiometric assay (IRMA), while the variability at low ferritin concentrations was significantly less with the EIA. Because only 10 microliter of serum is required for each assay, duplicate measurements can be performed on a single capillary tube of blood. When an automatic microtiter plate reader for optical density measurements is used, 80-100 duplicate determinations can be completed by one technologist in a single working day.

Effect of IgG anti-Rho(D) in adult patients with chronic autoimmune thrombocytopenia.

Abstract: Seventeen adult patients with chronic (15 cases) or acute (two cases) autoimmune thrombocytopenia (ITP) were given intravenous and/or intramuscular injections of 0.75-4.5 mg of IgG anti-Rho(D) over a period of 1-5 days. Significant elevations of the platelet count (increments greater than 50 X 10(9)/liter) resulted in 13 of 15 Rh-positive patients but not in either of two Rh-negative patients. Heat-aggregated human albumin given to one of the Rh-negative patients also did not lead to a significant increase of the platelet count. The elevation of the platelet counts in Rh-positive patients after IgG anti-Rho(D) administration was often transient (less than 4 weeks), but long-term benefit (greater than 5 months) was achieved in five cases. The IgG concentration on RBC from five Rh-positive patients studied increased from a usually undetectable value before to approximately 700-1,700 IgG molecules/per RBC after anti-Rho(D) administration resulting in a strongly positive direct antiglobulin test. Nevertheless, an overt clinical hemolysis was seen in only one patient. The clearance of autologous 51Cr-labeled RBC was determined in four patients and was slightly enhanced in three and normal in one splenectomized patient. We conclude that the Fc receptor blockade involved in platelet sequestration was not associated with the induction of significant RBC clearance and that a reversible interaction of sensitized RBC with phagocytic cells and/or a low-grade destruction of these cells might be sufficient for the elevation of circulating platelets in the majority of patients with ITP.

Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation

Abstract: The influence of cardiopulmonary bypass on fibrinolytic activity was assessed by a sensitive clot lysis assay in eight patients undergoing coronary artery bypass operations. Fibrinolytic activity increased immediately after cardiopulmonary bypass was begun and remained elevated throughout the period of extracorporeal circulation. At the conclusion of the operative procedure, fibrinolytic activity returned to the normal range in all patients, and no subject had postoperative bleeding.

Human parvovirus and aplastic crisis in chronic hemolytic anemias: A study of 24 observations

Abstract: From March 1984 through November 1985, 24 children and adults with aplastic crises were admitted in several Parisian hospitals. Twelve patients had known hemolytic anemia. Aplastic crisis revealed hemolytic anemia in the remaining patients. The detection of human parvovirus antigen was performed by counter-immunoelectrophoresis, and specific IgM antibodies were detected by IgM-antibody-capture-radioimmunoassay, in order to establish the incidence of human parvovirus infection in the genesis of the aplastic crisis. Twenty-one patients had acute infection with human parvovirus. In the three remaining patients, no marker of human parvovirus infection was found. The features of the human parvovirus linked aplastic crisis are described. We consider that human parvovirus infection, and unknown hemolytic anemia, must be systematically researched in any case of unexplained acute aplastic anemia.

Thrombocytopenia in homosexual men

Abstract: The office records of two private practices with a preponderance of homosexual patients were reviewed for cases of males with unexplained thrombocytopenia. Twenty-five patients meeting the selection criteria were found. The clinical and laboratory features of these patients were reviewed and compared to those characteristically seen in classic autoimmune thrombocytopenic purpura. The mean age of the group was 36.5 years. There was a high incidence of a history of sexually transmitted diseases. Sixty percent had another hematologic abnormality in addition to thrombocytopenia. The clinical outcomes for these 25 patients were as follows: eight (32%) had a spontaneous increase in platelets; four (16%) had a stable count not requiring therapy; 12 (48%) received high-dose prednisone; seven (28%) failed prednisone therapy and went on to splenectomy; two (8%) subsequently developed CDC-defined AIDS.

Erythrocyte incorporation of ingested stable isotope of iron (58Fe).

Abstract: Because of a possible hazard from the use of radioisotopes to determine iron absorption by infants, the use of stable isotopes for this purpose has much appeal. We have applied the method of inductively coupled plasma mass spectrometry (ICP/MS) to determine the mass ratio, 58Fe/57Fe, in blood before and after oral administration of 58Fe. From the increase in erythrocyte enrichment with 58Fe, we have calculated percentage absorption of iron. We have shown that the coefficient of variation of measured mass isotope ratio is 0.1-1.0%, depending on the conditions of the measurement. The method has been applied to a feasibility study involving four infants. Each infant was given 58Fe either as a single dose or as one dose on each of two consecutive days. Each dose provided 1.945 mg iron and 1.440 mg 58Fe. Samples of blood were obtained before isotope administration and at 14, 42, and 60 days thereafter. Isotopic analysis of the samples demonstrates that this approach results in a sufficiently large isotope enrichment to permit satisfactory measurement of iron availability. It is concluded that this new method is highly promising for studies of iron availability in infants and children.

Is sickle cell crisis a thrombotic event

Abstract: Although large vessel thrombi are occasionally reported in patients with homozygous sickle cell disease, the role of intravascular coagulation in typical pain crises is controversial. Therefore, we studied 24 sickle cell patients during and between episodes of pain crisis, using several sensitive tests of hemostasis. Fibrinogen was measured by a clotting assay, beta-thromboglobulin (beta-TG) and fibrinopeptide A (FPA) were quantitated by radioimmunoassay, and protein C was determined by absorbing the zymogen from test plasma, activating it with thrombin-thrombomodulin complex, and measuring activity with a selective synthetic substrate. Fibrinogen was elevated in asymptomatic patients (355 +/- 145 mg/dl) but was no different from the value in these same patients during crisis (333 +/- 180 mg/dl, p greater than 0.1). Similarly, beta-TG 136 +/- 52 ng/ml vs 118 +/- 56; FPA 3.7 +/- 4.8 ng/ml vs 5.2 +/- 4.5, and protein C 71 +/- 20% vs 66 +/- 19 showed no important changes during crisis. However, all these values were significantly different from those in age- and sex-matched healthy controls. beta-TG, fibrinogen, and FPA were elevated (p less than 0.001, 0.005, and 0.05, respectively), and protein C was decreased (p less than 0.003). We conclude that while chronic intravascular coagulation is common in patients with sickle cell disease, there is no evidence that the pain crisis per se is a thrombotic event.

Hematologic malignancy in sickle cell disease: Report of four cases and review of the literature

Abstract: Hematologic malignancy has rarely been reported in adults with sickle cell disease. We describe four sickle cell patients (two with hemoglobin SC, two with hemoglobin SS) who developed hematologic malignancy (acute myeloblastic leukemia, multiple myeloma, malignant histiocytosis, and Hodgkin's disease). Three of the cases represent the first adult association between SC or SS hemoglobinopathy and the particular malignancy involved. Sickle hemoglobin does not appear to exert a protective effect against childhood hematologic malignancies, suggesting that better survival in sickle cell disease may be accompanied by an increased incidence of hematologic neoplasms in adulthood. Karyotypic analysis revealed alterations of chromosome 5 in two sickle cell patients with leukemia, raising the possibility of a chromosomal link between the two diseases. Further epidemiologic and cytogenetic studies are needed to define the relationship between hematologic malignancy and sickle cell disease.

Post-transfusion purpura: a report of five patients and a review of the pathogenesis and management.

Abstract: We report five cases of post-transfusion purpura. Despite having profound thrombocytopenia, their management consisted only of steroid administration if serious bleeding was present. In one patient without bleeding, no specific therapy was given. This patient recovered uneventfully. Two patients died. One of these died from complicating illnesses rather than bleeding. The other suffered brain death, the result of a ruptured cerebral aneurysm. Four patients were PLA1 negative. The fifth patient had an antibody to an unidentified platelet-specific antigen.

Procedures for the inactivation of viruses in clotting factor concentrates.

Abstract: A considerable body of data has accumulated on the viral inactivated clotting factor concentrates. This information strongly indicates considerable safety and expected efficacy of these products. Probably most procedures are capable of inactivating large amounts of the LAV/HTLV-III virus, but there is considerable variability between products in the ability to inactivate the hepatitis viruses and perhaps also the LAV/HTLV-III. This variability is probably related to the mechanism of viral inactivation, the time of exposure to heat or chemical additives, and also the presence and type of stabilizer. So-called "second-generation" products will probably show improved elimination of more resistant viruses including the non-A, non-B forms.

Trisomy 1q in polycythemia vera and its relation to disease transition.

Abstract: Clinical and cytogenetic details of 12 patients with polycythemia vera and complete or partial trisomy of the long arm of chromosome 1 are reported. All patients had trisomy for at least the segments 1q22 to 1qter. The 1q or material from 1q was translocated to another chromosome in eight patients. This was chromosome 9 in four patients, and those cases all had trisomy also for 9p. The trisomy 1q was found at the time of diagnosis in three patients, later during the polycythemic phase in five, and in four patients when they were first examined during a late stage of the disease. Acute leukemia or a myelodysplastic syndrome developed in eight of the 12 patients. Signs of advanced disease, eg, myeloid metaplasia or myelofibrosis, preceded the leukemia in four cases and was noted in one more patient. Trisomy 1q was the most frequent structural chromosome abnormality in patients with polycythemia vera. It is thus one of several nonrandom abnormalities that can appear at any stage of the disease. It seems to occur with higher frequency in patients with myelofibrosis and/or leukemia, but it is not a specific characteristic of these complications.

Excessive fibrinolysis in suspected amyloidosis: demonstration of plasmin-α2-plasmin inhibitor complex and von Willebrand factor fragment in plasma

Abstract: We performed a hemostatic evaluation in detail in a patient with suspected amyloidosis who was suffering from several bleeding episodes. He had a shortened euglobulin clot lysis time, decreased alpha 2-plasmin inhibitor (alpha 2-PI), decreased plasminogen, elevated tissue-type plasminogen activator (t-PA), elevated plasmin-alpha 2-PI complex, and decreased ratio of ristocetin cofactor to von Willebrand factor (vWF) antigen. Fibrinogen and fibrin/fibrinogen degradation products levels fluctuated, with abnormal values on several occasions. On crossed immunoelectrophoresis, plasmin-alpha 2-PI complex and vWF fragment were demonstrated in the patient plasma. These abnormal findings and bleeding symptoms improved following the administration of tranexamic acid. Discontinuation of tranexamic acid resulted in deterioration of these parameters. These observations indicate that pathologic fibrinolysis (continuous intravascular plasmin generation) characterized by the consumption of alpha 2-PI and plasminogen, formation of plasmin-alpha 2-PI complex, and fragmentation of vWF contributed to the bleeding in this patient. It is important to recognize excessive fibrinolysis as the underlying cause of bleeding in these patients, since specific treatment with antifibrinolytic agents is effective in controlling the bleeding.

Comparative evaluation of bone marrow aspirate particle smears, biopsy imprints, and biopsy sections.

Abstract: Bone marrow aspirate particle smears, biopsy imprints, and biopsy sections were compared to determine the accuracy of the three samples in assessing for overall cellularity, differential cell count, megakaryocyte density, iron stores, and tumor infiltration. Aspirate particle smears and biopsy imprints were stained by Wright-Giemsa method. Aspirate particle smears were also stained with Prussian-blue. Biopsy sections were 1 1/2–2 μ thick and were prepared from non-decalcified plastic embedded samples and stained with combined Prussian-blue-hematoxylin-eosin, and Giemsa. One hundred-eight sets of specimens from 99 patients were examined. In 20 cases, chi-square analysis showed a comparable degree of cellularity (p 0.05). Monocytes did not correlate in any of the groups (p > 0.05). In 47 cases, chi-square analysis of iron stores in the aspirate particle smears correlated well with those in the biopsy sections (p < 0.001). Fifty-two marrows that were done for staging nonhematological malignancies revealed malignant cells in 21 cases, biopsy sections were positive in all, biopsy imprints were positive in 19 (90%), and aspirate particle smears were positive in 7 (33%). Thirty-six marrows done for staging non-Hodgkin's lymphoma showed malignant cells in 13 cases. Twelve (92%) biopsy sections, three (23%) biopsy imprints, and nine (69%) aspirate particle smears contained lymphoma cells. In conclusion, a satisfactory evaluation of marrow samples for diagnostic studies can be achieved by examination of biopsy sections along with aspirate particle smears or biopsy imprints. Any of the three marrow preparations alone is not sufficient for accurate diagnosis in all cases. The biopsy imprint is an accurate modality for identifying nonhematological tumor metastasis in the bone marrow.

The effects of splenectomy on engraftment and platelet transfusion requirements in patients with chronic myelogenous leukemia undergoing marrow transplantation.

Abstract: Granulocyte and platelet recovery as well as platelet transfusion requirements following allogeneic marrow transplantation were analyzed in 67 patients with chronic myelogenous leukemia in the chronic phase. Twenty patients had splenectomy prior to transplantation. Forty-seven patients were transplanted without splenectomy, 21 of whom had splenic enlargement by physical examination. There were no differences in the proportion of patients with granulocyte recovery, but the recovery of peripheral granulocytes to levels of 200, 500 and 1,000/mm3 occurred more rapidly in the splenectomy group than in the no-splenectomy group. Patients with splenectomy received platelet transfusions for a mean of 10 (2–36) days as compared to 20 (3–82) days for patients without splenectomy (p < .001). Eighteen (90%) patients with splenectomy became platelet transfusion independent at a median of 16 (2–32) days after transplantation as compared to 40 (85%) patients without splenectomy who became transfusion independent at a median of 28 (15–86) days (p < .001). The proportion of patients achieving platelet levels of 50 and 100 × 103/mm3 did not differ between the two groups (p = .07), but patients in the splenectomy group achieved these levels more rapidly following transplant (p < .001). One of 17 evaluable patients in the splenectomy group and 31 of 46 in the no-splenectomy group became refractory to random platelets (p < .001) and required platelets from family members or unrelated completely or partially HLA matched donors. In the no-splenectomy group, splenic size did not affect the speed of granulocyte or platelet recovery or platelet transfusion requirements. There was no difference in the post-transplant survival of patients with or without splenectomy.

Leukapheresis for control of chronic myelogenous leukemia during pregnancy

Abstract: Leukapheresis was used as the sole modality of treatment of a patient with chronic myelogenous leukemia (CML) during her pregnancy The specific requirements for safe leukapheresis during pregnancy are discussed, and the literature describing the management of CML during pregnancy is reviewed Leukapheresis may be the treatment of choice in selected pregnancy patients with CML since it avoids the potential teratogenic effects of chemotherapy or radiation therapy

Post-transfusion purpura associated with alloimmunization against the platelet-specific antigen, baka

Abstract: Post-transfusion purpura (PTP) with severe thrombocytopenia occurred eight days after transfusion in a 28-year-old woman and responded to treatment with prednisone and plasma exchange In contrast to nearly all previously studied cases of PTP, the patient's platelets were PIAI-positive and anti-PIAI antibody could not be detected in serum obtained during the thrombocytopenic episode Her serum was found to contain an antibody specific for a recently described platelet-specific alloantigen, Baka, in addition to multiple HLA-specific antibodies The patient's platelets, typed following recovery, were Baka-negative These findings indicate that post-transfusion purpura can occur in association with alloimmunization to platelet-specific antigens other than PIAI In performing the serologic studies, a close relationship and possible identity between Baka and another recently reported platelet antigen, Leka, was observed A method for analyzing mixtures of cytotoxic platelet-reactive antibodies without separating the individual antibodies is described

Autoreactive erythroid progenitor‐T suppressor cells in the pure red cell aplasia associated with thymoma and panhypogammaglobulinemia

Abstract: In vitro erythroid culture studies and lymphocyte markers were performed in a patient with a spindle cell thymoma who developed red cell aplasia, panhypogammaglobulinemia, and multiple opportunistic infections. At the time of presentation, erythroid progenitor cells (CFUe, BFUe) were markedly reduced when cultured from marrow mononuclear cells. Removal of T cells from bone marrow mononuclear cells by E-rosetting or complement-mediated lysis with OKT3 pan T cell monoclonal antibody increased growth of erythroid progenitor cells in vitro. Readdition of bone marrow or pleural fluid T cells derived from the thymoma suppressed autologous, but not allogenic, erythroid progenitor cell (CFUe, BFUe) proliferation in vitro. The erythroid progenitor suppressor T cells were predominantly OKT11+, OKT3+, OKT8+ and Ia+ consistent with activated suppressor T cells. Treatment of the patient with cyclophosphamide and corticosteroids reduced marrow lymphocytes fourfold, and a prompt reticulocytosis ensued. After recovery, erythroid progenitor cells were easily detectable. These studies provide new evidence for T cell-mediated suppression of erythropoiesis in a unique subset of patients with red cell aplasia associated with thymoma and hypogammaglobulinemia.

The distribution of lysozyme, alpha‐1‐antitrypsin, and alpha‐1‐antichymotrypsin in normal hematopoietic cells and in myeloid leukemias: An lmmunoperoxidase study on cytocentrifuge preparations, smears, and paraffin sections

Abstract: Blood and bone marrow samples from 20 individuals with reactive conditions and 26 cases of acute and chronic myeloid leukemias were tested for the presence of lysozyme, alpha-1-antitrypsin (α-1-AT), and alpha-1-antichymotrypsin (α-1-ACT). We compared the reactivity of samples in smears, cytocentrifuge preparations, and paraffin sections. Lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin were found only in polymorphonuclear leukocytes and monocytes and their precursors. Lymphocytes, Erosetting cells, Con A-activated lymphocytes, natural killer (NK) cells, red blood cells, erythroblasts, and megakaryocytes were consistently negative. Leukemic myeloblasts showed definite reactivity for both alpha-1-antitrypsin and α-1-ACT, but not for lysozyme. By contrast, lysozyme was present in poorly differentiated leukemic monoblasts, while alpha-1-antitrypsin and alpha-1-antichymotrypsin showed only weak reactivity. More mature myeloid and moncytic cells showed positive staining for all three antigens tested with differences in staining distribution and intensity. In four cases of chronic myeloid leukemia (CML), circulating mature polymorphonuclear leukocytes were deficient in both lysozymne and alpha-1-antitrypsin. The use of lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin identifies normal and leukemic cells of the myeloid-monocytic series at all stages of maturation and is applicable to a variety of sample preparations.

Acquired von Willebrand disease and storage pool disease in chronic myelocytic leukemia

Abstract: Platelet function was evaluated in 20 patients with chronic myelocytic leukemia (CML), all Ph positive. Seven showed abnormal epinephrine-induced aggregation, while four had impaired both ADP- and collagen-induced aggregation. The platelets of all patients aggregated with arachidonic acid, thus ruling out cyclooxygenase or lipoxygenase deficiency. The intracellular concentrations of ATP and ADP were significantly below normal, and the ratio of ATP/ADP was greater than normal in all 12 patients. ATP released from platelets by Lumi-aggregometer was reduced. In four patients with abnormal ristocetin-induced aggregation, vWF:Ag, RCoF, and FVIII:C were all reduced. No significant inactivation of factor VIII was induced in normal plasma by incubation with patient's plasma. The crossed immunoelectrophoretic analysis revealed that vWF:Ag in these patients was mainly composed of more anodic component as compared with that of normal plasma. The ratio of vWF:Ag/RCoF was significantly greater than normal. A marked increase of factor VIII and a rapid return of vWF:Ag and RCoF to the baseline after the 1-deamino-8-arginine vasopressin (DDAVP) infusion were observed. Transient increase in vWF:Ag after the infusion of DDAVP appeared with less anodic forms and in the same relative proportion as that in normal plasma. The present study shows that in some patients with CML storage pool disease occurs with acquired von Willebrand disease.

High‐dose cytosine arabinoside in the treatment of preleukemic disorders: A leukemia intergroup study

Abstract: Fifteen patients with myelodysplastic/myeloproliferative disorders were treated with high-dose cytosine arabinoside therapy While severe toxicity was produced in every patient, only two of the 15 patients entered complete remission and two achieved partial remission status The therapeutic responses were confined to patients who had severe myelofibrosis of apparently recent onset

DDAVP in acquired von Willebrand syndrome associated with multiple myeloma

Abstract: The response to a single intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP, desmopressin) was studied in two patients with acquired von Willebrand syndrome associated with IgG-kappa myeloma. Following infusion of DDAVP (0.3-0.4 micrograms/kg), prolonged bleeding time was normalized; plasma ristocetin cofactor activity, von Willebrand factor antigen, and factor VIII activity were remarkably increased; and high-molecular-weight forms of von Willebrand factor were demonstrated by crossed immunoelectrophoresis in both patients. Excellent hemostasis was achieved following administration of DDAVP in one patient when it was used for the treatment of gum bleeding and for the prophylaxis of bleeding during and after dental extractions. These observations suggest that DDAVP is an effective alternative to blood products for at least some patients with acquired von Willebrand syndrome in addition to patients with inherited von Willebrand disease, hemophilia A, and uremia.

Primary lymphomas of the small intestine: east-west contrast.

Abstract: Primary small intestinal lymphoma (PSIL) represents a heterogenous group of disorders with variable clinical and pathologic features and a characteristic age, socioeconomic, and geographic distribution. In developed countries, PSIL usually occurs as a localized ileal tumor, shows a bimodal age distribution, and most frequently presents with abdominal pain and obstructive symptoms. Histologicaily, most of these tumors are diffuse histiocytic, lymphocytic, or undifferentiated lymphomas. Other variants of PSIL, collectively referred to as immunoproliferative small intestinal disease, occur most often among young patients of poor socioeconomic status in Third World countries, mostly in the Middle East and Mediterranean area. They are characterized by involvement of long loops of the upper small intestine and commonly present with abdominal pain, diarrhea, malabsorption, and clubbing of the fingers. A subgroup of these patients shows a serological abnormality with the appearance of part of the alpha heavy chain of IgA in the serum. Histologically, the lesion appears as a dense diffuse lymphoplasmacytic infiltrate of the mucosa of the upper jejenum or duodenum. A form of malignant lymphoma of true histiocytic origin complicates long-standing celiac disease. The contrasting clinical, epidemiological, histopathological, and immunological features of these variants of PSIL raise interesting questions about the pathogenesis of small bowel lymphoma.

Thrombotic thrombocytopenic purpura subsequent to acute myelogenous leukemia chemotherapy

Abstract: A woman in complete remission from acute myeloblastic leukemia developed thrombotic thrombocytopenic purpura (TTP) subsequent to the third intensive consolidation cycle of cytosine arabinoside and daunorubicin chemotherapy. The constellation of clinical manifestations indicative of TTP were recognized only in retrospect, as they were initially attributed to more usual complications of bone marrow-ablative chemotherapy. The manifestations, probably fueled by numerous red cell and platelet transfusions, increased at the time of recovery of hematopoiesis. At postmortem examination, characteristic microvascular lesions were found in most organs. Similar thrombotic microangiopathy has been described with mitomycin-based chemotherapy regimens and with the combination of cisplatin, vinblastine, and bleomycin. Successful management of this serious complication of chemotherapy requires increased awareness and earlier recognition.

Immunoregulatory abnormalities in myelodysplastic disorders.

Abstract: Immunoregulation was assessed in a group of patients with myelodysplasia (MDS) by flow cytometric analysis of peripheral blood lymphocyte subsets and in vitro studies of mitogen-stimulated T-lymphocyte blastogenesis. Mitogenesis was significantly depressed in MDS patients compared to controls (p less than .001) and a similar defect was found in a small group of patients with untreated acute nonlymphocytic leukemia (ANLL) (p less than .005). The impaired mitogenic response ability of T-cells in these patients did not appear to be the result of alteration in lymphocyte subpopulation ratios. The observed defect might result from defective cooperation between T-lymphocytes and abnormal myeloid elements. Alternatively, the lymphocytes themselves could be derived from the abnormal clone and thus be functionally abnormal.

Unbalanced 1;7 translocation and therapy-induced hematologic disorders: a possible relationship.

Abstract: An identical chromosome abnormality, which appears to be derived from a 1;7 translocation [ +der(1), t(1;7)(p11;p11)], was observed in the bone marrow of 12 patients with various hematologic disorders at the Mayo Clinic from 1980 to 1984. At the time of cytogenetic evaluation, nine of the patients had either a myeloproliferative disorder or a myelodysplastic syndrome, one had an acute leukemia, and two had treated multiple myeloma with no morphologic evidence of evolving myeloproliferative disease. Of the 11 patients for whom information about previous therapy was available, seven had a history of exposure to chemotherapy for a previous malignant disorder; we were unable to establish whether the remaining patient had had prior treatment. This study suggests a possible relationship between +der(1), t(1;7)(p11;p11) and some treatment-induced hematologic disorders. Such chromosome abnormalities may be the result of a reciprocal chromatid translocation and adjacent I segregation of a quadriradial configuration in metaphase.

Spα1/65 hereditary elliptocytosis in North Africa

Abstract: The Sp alpha I/65 variant of the spectrin has been recently described in black people with hereditary elliptocytosis (HE). The present study reports on a similar Sp alpha I/65 variant in nine North African persons belonging to four unrelated families. The abnormality was associated with a variable degree of elliptocytosis. In one case, red cell morphology was normal. In the nine carriers of the biochemical abnormality, the spectrin dimer self-association was defective. The association constant was reduced: 0.65 to 1.7 X 10(5) M-1 (controls: 4.6 +/- 0.5 X 10(5) mM-1 (n = 21)); in six cases, there was a higher level of spectrin dimer in the low ionic strength extract at 4 degrees C: 13.0 to 19.7% (controls: 6.4 +/- 2.1% (n = 7)). Limited tryptic digests of spectrin from the nine persons revealed a decrease of the 80,000-dalton alpha-1 domain, and the concomitant appearance of a peptide with a molecular weight of 65,000 daltons and an isoelectric point ranging from 5.0 to 5.1. There was a correlation between the proportion of the 65,000-dalton fragments, the defect of spectrin self-association, and the extent of morphological alteration. This is the first large series concerning a spectrin abnormality in non-black persons. In North Africa, cases of HE that are not due to a protein 4.1 defect have turned out so far to be associated with the Sp alpha I/65 variant.

Treatment of myelodysplastic syndrome with 1.25‐dihydroxy‐vitamin D3

Abstract: 1.25-dihydroxy-vitamin D3 (1.25 (OH)2D3) was tested in seven patients with myelodysplastic syndrome. The study was undertaken because 1.25 (OH)2D3 promotes differentiating myeloid cells in vitro and because of a prior report of potential benefit in a clinical study. The drug was given orally at a dose of 2.5 micrograms/day for a minimum of 8 weeks (range 8-28). After therapy, there were no significant changes in any of the parameters observed in peripheral blood or bone marrow. We did not observe any feature of granulocytic-monocytic differentiation. Treatment was well tolerated. One patient died because of bone marrow failure. Survivors have persisting myelodysplastic syndrome and continue to be transfusion dependent. 1.25 (OH)2D3 has no beneficial effect in patients with myelodysplastic syndrome with this dose regimen.

Pure red cell aplasia: response to therapy with anti-thymocyte globulin.

Abstract: Pure red cell aplasia (PRCA) results from the failure of erythrocyte differentiation and may respond to immunosuppressive therapies. We have treated nine patients with PRCA refractory to steroids and/or cyclophosphamide with anti-thymocyte globulin (ATG). Six patients had normal numbers of erythroid bursts (from erythroid burst-forming units) or erythroid colonies (from erythroid colony-forming units) detectable in vitro, and all responded to therapy with ATG. In vitro studies suggested T-cell inhibition of erythropoiesis in four of these six patients and humorally mediated erythroid suppression in one. In three individuals, virtually no erythroid progenitors were detected in marrow culture. None of these patients responded to ATG. Myelofibrosis, 5q- chromosomal abnormality, or the subsequent development of thrombocytopenia in these individuals suggested that PRCA resulted from an intrinsic stem cell disorder. Our studies demonstrate that ATG is effective therapy for PRCA, and it may be especially useful in children or other patients in whom alkylating agents are not appropriate. We also confirm that erythroid growth in marrow culture predicts those patients who will respond to ATG or other immunosuppressive therapies.

Hepatitis B vaccination of 113 hemophiliacs: Lower antibody response in anti‐LAV/HTLV‐III‐positive patients

Abstract: One-hundred thirteen adults and children with hemophilia or other congenital bleeding disorders were vaccinated against the hepatitis B virus. Each patient was given three subcutaneous injections of the vaccine at monthly intervals and then a fourth booster dose 14 months after the first. The vaccine was highly immunogenic, since 111 of 113 patients (98%) produced anti-HBs (10 mIU/ml or more). After the first three vaccine doses and after the booster dose, ten anti-LAV/HTLV-III-positive hemophiliacs produced anti-HBs but had a lower average titer than anti-LAV/HTLV-III-negative hemophiliacs. Of the 23 patients treated with concentrates in the 15 month postvaccination period only, none acquired HBV infection. Of the 50 patients treated with concentrates also in the 6 month prevaccination period, one developed hepatitis B. In summary, the vaccine was highly immunogenic in both children and adults with hemophilia; anti-LAV/HTLV-III-positive patients responded to the vaccine, but the average anti-HBs response was lower; no case of hepatitis B occurred in patients treated with concentrates only in the postvaccination period.