American Journal of Hematology

doi: 10.1002/ajh.2830220401pmid: N/A

Macfarlane, S. D.; Tauro, G. P.

doi: 10.1002/ajh.2830220402pmid: 3460326

Bone marrow necrosis has been regarded as an indicator of very poor prognosis in malignant disease. The cause and incidence are unknown, and reports of treatment response are few. We describe four children with marrow necrosis at presentation with acute lymphocytic leukemia (ALL), all of whom entered remission with standard treatment showing complete marrow healing. The bleak outlook for patients with marrow necrosis based on early experience in adults with disseminated malignancy does not appear to apply to children with ALL. The incidence of marrow necrosis at diagnosis of childhood ALL is 1%.

Marx, Gerard; Hopmeier, Pierre

doi: 10.1002/ajh.2830220403pmid: 3728455

Physiologic concentrations of Zn(II) (4–40 μM) can increase the rate of thrombin‐induced fibrin clot formation (decreased clotting time, CT) and increase the turbidity of the fibrin gel. Both the initial and ultimate turbidity (Abs600 mm) of fibrin gels are increased in the presence of Zn(II). Two techniques were used to elaborate the mechanisms of Zn+2 procoagulant effect. Analytical ultracentrifugation indicates that Zn(II) does not induce the formation of fibrinogen multimers. Radioimmunoassay for FPA indicates that thrombin activation of fibrinogen is decreased by Zn(II), with 50% inhibition of FPA release observed at 35 μM Zn(II). These experiments indicate that the critical feature of Zn(II) procoagulant effect is not due to the induction of fibrinogen proteolysis by thrombin, which is actually decreased. Rather, it appears that Zn(II) accelerates the polymerization step of fibrin assembly and concomitantly modifies fibrin gel structure.

Kaplan, Joseph; Ravindranath, Yaddanapudi; Inoue, Susumu

doi: 10.1002/ajh.2830220404pmid: 3487974

To determine the type and proportion of cases within that type of acute lymphoblastic leukemia (ALL) that has a natural killer (NK) cell phenotype, we examined leukemic blasts from 31 children with ALL (14 with T‐ALL, 17 with non‐T‐ALL) for expression of antigens detected by NK‐specific monoclonal antibodies Leu 11b, Leu 7, and 1G2 (an antibody we have developed that cross‐reacts with Leu 7). None of the patients had leukemic blasts that reacted with Leu 11b. However, leukemic blasts from four T‐ALL patients were 1G2+ and/or Leu 7+. Blasts from two of these had spontaneous lytic activity against standard NK target cell line K562; blasts from one killed K562 only when incubated with interferon; blasts from the other had no lytic activity against K562 but did manifest antibody‐dependent cell‐mediated cytotoxicity against antibody‐coated cells from NK‐resistant cell line SB. Blasts from all four Leu 7+ patients had L2 morphology. In one, the leukemic blasts had azurophilic cytoplasmic granules similar to those found in NK‐enriched normal populations of large granular lymphocytes. These findings suggest that a significant proportion of T‐cell acute lymphoblastic leukemias may be malignancies of NK cell origin.

Verdirame, Joseph D.; Bruckman, James E.; Feagler, John R.; Commers, James R.

doi: 10.1002/ajh.2830220405pmid: 3524202

Of the first 14 patients with acute or chronic leukemia to undergo bone marrow transplantation at our hospital, 9 (64%), all good‐risk, are still alive in remission at 18 to 42 months of follow‐up (mean, 29 months) with their Karnofsky performance status between 80% and 100%. The conditioning regimen of fractionated‐dose irradiation and high‐dose chemotherapy eradicated their disease; only two patients relapsed after transplantation. Toxicity was acceptable. Acute graft‐versus‐host disease developed in six patients (43%) (grade I or II in four, grade IV in two) and progressed to chronic graft‐versus‐host disease in four. Viral pneumonitis developed in three patients (21%), but none had idiopathic interstitial pneumonitis. The mean hospital charge was $54,355. These preliminary results suggest that good‐risk patients with acute or chronic leukemia can be treated with bone marrow transplantation in a university affiliated hospital with appropriate staff and support facilities and achieve results comparable to those in research institutions at a competitive cost.

Jacobs, Peter

doi: 10.1002/ajh.2830220406pmid: 3460327

In a pilot study, 21 consecutive and previously untreated adults with chronic granulocytic leukaemia received either busulphan (group 1: n = 11) or a combination of the epipodophyllotoxin VP16‐213 with cytosine arabinoside and doxorubicin (group 2: n = 10). Using a standardised protocol, objective response, defined as a granulocyte count consistently less than 10 × 109/1 with no clinical evidence of the disease, was achieved in 45 and 40% of the patients, respectively, and median survivals were 89 and 107 weeks (p > 0.05). Although there was no difference in morbidity, the study was discontinued because the combination chemotherapy was more complex to administer, was associated with greater patient inconvenience, and offered no advantage over single‐agent therapy in managing the stable phase of chronic granulocytic leukaemia.

Pasquale, Donald; Chikkappa, G.

doi: 10.1002/ajh.2830220407pmid: 3728456

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 < 0.001) and megakaryocyte density (p < 0.001) among the three preparations. Differential count comparison by regression analysis indicated that mean percentages of neutrophilic cells in the proliferation compartment were comparable in the three groups (p < 0.01). A better correlation was obtained among the three groups in the percent neutrophilic cells in the maturation‐storage compartment, normoblasts, eosinophils, and plasma cells (p < 0.001). Lymphocytes in the aspirate smears correlated with the biopsy imprints (p < 0.01) but not with the biopsy sections (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.

Mohri, Hiroshi

doi: 10.1002/ajh.2830220408pmid: 3487975

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.

Macfarlane, S. D.; Tauro, G. P.; Rendall, K.; Welch, J. J.; Ekert, H.

doi: 10.1002/ajh.2830220409pmid: 3728457

A technique for examining relatively large volumes of bone marrow for involvement by malignancy is described. The use of discontinuous Percoll gradients offers no advantage over conventional methods in the diagnosis of hematological malignancy. Its usefulness in detecting infiltration by solid tumor is uncertain. Complete exclusion of malignancy from the fraction containing hematologic stem cells in three patients raises the possibility that this technique is a useful adjunct to other methods of marrow purging before autologous marrow rescue in malignant disease.

Etzioni, A.; Atias, D.; Pollack, S.; Levy, J.; Vardi, P.; Hazani, H.; Benderly, A.

doi: 10.1002/ajh.2830220410pmid: 2425618

A 10‐year‐old girl with multiple endocrinopathies, hypoparathyroidism, and pernicious anemia subsequently developed pure red cell aplasia, which responded only temporarily to cytotoxic therapy. Because of transfusion dependency, resistance to steroids, plasmapheresis, and Cytoxan, she was given injections of intramuscular gammaglobulin. The injections caused a prompt and sustained rise in the child's erythropoiesis.