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Hopper, John E.; O'brien, Jamie; Papagiannes, Elaine
doi: 10.1002/ajh.2830290302pmid: 3142253
The culture supernatant immunoglobulin (CSIg) of blood mononuclear cells (MNCs) from 14 patients with chronic lymphocytic leukemia (CLL) was determined using a panel of. nanogram‐sensitive radioimmunoassays that measured IgM, IgG, IgA, total K‐lg, and total λ‐lg. Bone marrow cells from three patients were also cultured and the blood and marrow CSIg results were compared. The CSIg of 1‐day cultures was employed as a measure of shedded surface membrane lg (Smlg) for the 7‐ and 14‐day cultures. Adjusting for shedded Smlg, it was found that in resting unstimulated conditions, monotypic free light (L) chain was virtually the only identifiable secreted lg product in 12 of 14 blood MNC cultures and in three of three marrow cell cultures. In pokeweed mitogen (PWM)‐stimulated cultures, monotypic free L chain also dominated, except for significant polyclonal Ig secretion found in three cultures from residual normal blood MNCs. The secretion by CLL‐B cells of significant amounts of free L chain with a virtual absence of whole Ig raises important questions about the presence and function of phenotypically equivalent normal B cells in blood and bone marrow, and also the immunological role of secreted free L chain. Noting recent evidence that PWM‐stimulated normal blood MNCs secrete significant amounts of polyclonal free L chain, the argument is advanced that normal blood and bone marrow contain B cells of CLL‐B phenotype and that secreted free L‐chain‐bearing clonal idiotypic markers interact with autologous cells of the idiotypic regulatory network and possess a key role in the regulation of clonal growth and Ig synthesis.
Phillips, George; Slingluff, Craig; Hartman, John; Thomas, Patricia; Akwari, Onye
doi: 10.1002/ajh.2830290303pmid: 3189307
Totally implantable catheters (TICs) have recently been employed for long‐term central venous access in patients with sickle cell disease (SCD). We have reviewed our experience with 10 TICs inserted in patients with SCD. These were compared to 33 TICs inserted in patients without SCD (controls). The primary diagnosis was malignancy in most of the controls. The SCD patients experienced a marked increase in total complications (70 vs. 24%), as well as in complications requiring catheter removal (50 vs. 3%). No variable explained these differences except the presence of SCD. The complications requiring catheter removal from SCD patients were infections, catheter thrombosis, and venous thrombosis. The increased risk of these complications must be considered before a catheter is inserted; however, the average useful life of these catheters exceeded 12 months. They remained useful in the care of patients with poor venous access and multiple complications of SCD.
Letellier, Steven J.; Hunter, Jay B.; Aster, Richard H.
doi: 10.1002/ajh.2830290304pmid: 3189308
Studies of the inheritance of the platelet‐specific alloantigens PIA1/PlA2 and Baka/Bakb in informative families provided evidence that the genes determining PlA and Bak antigens are in close genetic linkage (P = .004). In 154 normal, unrelated Caucasian subjects it was found that the antigen PIA1 is associated with Baka and the antigen PIA2 with Bakb more often than would be expected by chance (P < .05). Bak and PIA antigens are carried on platelet membrane glycoproteins IIb and IIIa, respectively, which are decreased or absent in the inherited platelet disorder Glazmann's thrombasthenia. Thus, the findings suggest that the defect in this disease involves two closely linked genes.
Ozkaynak, M. Fevzi; Scribano, Philip; Gomperts, Edward; Izadi, Parvin; Millin, Rachel; Jr, Hart Isaacs; Ettinger, Lawrence J.
doi: 10.1002/ajh.2830290305pmid: 3189309
Bone marrow cellularity estimated by biopsy was compared to the cellularity of the aspirate particle smear and the volumetric method in two groups of children. In the first group, 101 consecutive bone marrow biopsies and aspirates were evaluated from patients with various diagnoses. In the second group, 20 patients with acute nonlympho‐blastic leukemia were studied with 80 biopsies and aspirates at diagnosis and following chemotherapy. A wide discrepancy was noted between bone marrow cellularity confirmed by biopsy vs. the particle smear or the volumetric method in both groups. Neither the volumetric nor the particle method provides a good correlation of bone marrow cellularity. We also compared the volumetric method with that of the biopsy to evaluate the efficacy of the former method in detecting bone marrow infiltration by solid tumors. The volumetric method is an accurate modality of identifying solid tumor infiltration in the bone marrow.
Matsuo, Tatsuki; Jain, Nemi C.; Bennett, John M.
doi: 10.1002/ajh.2830290306pmid: 3189310
Leukemic cells of 43 patients with acute promyelocytic leukemia (M3) were investigated morphologically and cytochemically to determine the percentage of aberrant enzymes and whether or not the presence impacts on the clinical outcome. Twelve patients (27.9%) showed alpha‐naphythyl acetate esterase (ANAE) activity in their leukemic cells, and two of these cases revealed remarkably low myeloperoxidase (MPO) positivity, a pattern seen in monocytic precursors. However, further cytochemical evidence for this monocytic feature, the inhibition of naphthol AS‐D acetate esterase (NASDA) activity with sodium fluoride (NASDA‐F), was found in only five of these nine patients. In 31 cases (72.1%), there was minimal ANAE activity. Of interest, two of these were devoid of naphthol AS‐D chloroacetate esterase (CAE), which is prominently displayed in neu‐trophilic granulocytes, even though these leukemic cells were 100% intensely positive for MPO activity. Between the two groups with and without ANAE activity, there were no remarkable differences in the distribution of sex and age, hematological findings, and rates of complete response. Our study has confirmed the cytochemical heterogeneity of M3 with no obvious relationship between this heterogeneity and early therapeutic outcome.
Cheson, Bruce D.; Bennett, John M.; Rai, Kanti R.; Grever, Michael R.; Kay, Neil E.; Schiffer, Charles A.; Oken, Martin M.; Keating, Michael J.; Boldt, David H.; Kempin, Sanford J.; Foon, Kenneth A.
Ohyashiki, Junko H.; Ohyashiki, Kazuma; Shimizu, Hirofumi; Miki, Makoto; Kimura, Nobuhiro; Mori, Shigeo; Fujisawa, Kouji; Akatsuka, Jun‐Ichi; Toyama, Keisuke
doi: 10.1002/ajh.2830290308pmid: 3263797
We report an 8‐year‐old boy with Ph‐positive chronic myelogenous leukemia (CML) who showed a testicular tumor as the first manifestation of blastic crisis. Pathological examination of the excised testis revealed marked infiltration of immature cells, whereas bone marrow remained in the chronic phase. Immunohistochemical and molecular examinations disclosed the immature cells to have B‐lymphocyte surface determinants and immunoglobulin JH rearrangement. DNA obtained from the testis and peripheral blood cells showed similarly rearranged bcr configurations, indicating that infiltrating cells in the testis originated from the CML clone. Bone marrow showed B‐lymphoid blastic crisis 4 months after testicular involvement.
Dhingra, Kapil; Michels, Sheryl D.; Winton, Elliott F.; Gordon, David S.
doi: 10.1002/ajh.2830290309pmid: 3142254
We describe two patients who developed aplastic anemia early in the course of non‐A, non‐B hepatitis. Spontaneous rapid recovery of bone marrow function occurred in both patients. Although early bone marrow transplantation has been recommended as the treatment of choice in hepatitis‐associated aplastic anemia, these patients illustrate the need for a period of expectant observation before undertaking bone marrow transplantation in such patients.
Gómez‐Almaguer, David; Marfil‐Rivera, Javier; Kudish‐Wersh, Alex
doi: 10.1002/ajh.2830290310pmid: 3189312
Eight patients with idiopathic severe aplastic anemia received acyclovir as the initial treatment to ascertain if this antiviral therapy could be effective. Three patients showed improvement, but only one had a sustained recovery. The responses could be coincidental, but it seems that some patients can benefit from acyclovir. More studies are needed on the role of viruses and antiviral therapy in relation to severe aplastic anemia.
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The National Cancer Institute (NCI)‐sponsored Chronic Lymphocytic Leukemia (CLL) Working Group was convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials. We recognized the previous efforts in 1967 published again in 1973 as the report of the Chronic Leukemia‐Myeloma Task Force (1) and 1978 of Cancer and Leukemia Group B (CALGB) (2). We have used these reports for guidance during the current effort. Several noteworthy developments in the past few years have made it necessary to modify the previous guidelines. First, the diagnostic criteria for CLL and its clinical staging have been developed and well defined. Second, although staging systems facilitated entry of comparable and relatively homogeneous groups of patients in clinical trials, the definitions of response (CR) and partial response (PR) were not uniformly adopted from the previous guidelines in the clinical trials (Tables IA, IB); therefore, comparisons of results obtained in different studies became difficult. Third, there has been an improvement in our understanding of the immunology and biology of CLL. Finally, we are witnessing the emergence of several chemotherapy agents that promise impressive activity in CLL (e.g., 2′‐deoxycoformycin (3), fludarabine monophos‐phate (4,5)), and thereby offer the potential for improving survival time in this disease. To best identify regimens worthy of continued pursuit in large comparative trials, standardized guidelines for evaluation are essential. A number of laboratory investigations are also presented for which scientific interest is high yet relevance remains to be determined; thus, they are presented as companion studies to the clinical trials. This mechanism allows for flexibility in the testing of these questions and for additional ideas in the future without requiring modification of an entire treatment protocol.