Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression

Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible.     

High dose carboplatin/VP-16 plus ifosfamide with autologous bone marrow support in the treatment of refractory germ cell tumors.

We report seven patients with germ cell tumors which either recurred following a minimum of two regimens of platinum-based chemotherapy or were refractory to cisplatin. The patients were treated with one or two courses of high dose carboplatin (CBDCA) and etoposide (VP-16) plus ifosfamide (IFX) with mesna uroprotection and autologous bone marrow support. The doses given were CBDCA 500 mg/m2 every other day x 3 and VP-16 400 mg/m2 every other day x 3. IFX was given in a dose of 2 g/m2 daily x 5 days with mesna. The original intent of the protocol was to explore escalating doses of IFX, but excessive renal toxicity at the first dose level prevented escalation. Of the seven patients treated, four developed a marked decline in their renal function and three of the four required hemodialysis or hemofiltration. Six of seven patients treated had a decline in their serum markers indicating a response to therapy, but all have relapsed. Our conclusion is that while the combination of CBDCA/VP-16/IFX with ABMT is active in this group of patients, it is associated with excessive renal toxicity which is probably due to underlying renal dysfunction secondary to extensive prior cisplatin-based chemotherapy.     

Recombinant human colony stimulating factor-granulocyte/macrophage and -granulocyte,but not macrophage induce the development of a respiratory burst in primary human myeloid leukemic cells in vitro

Summary Respiratory burst develops in myeloid blast cells if they differentiate functionally along the monocytic or granulocytic lineage. Using the nitroblue tetrazolium (NBT) assay we studied the effects of recombinant human granulocyte/macrophage colony stimulating factor (rhuGM-CSF), rhuG-CSF and rhuM-CSF on development of respiratory burst activity in primary blast cells from patients with myeloid leukemia. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (AML, n=13) or myeloidblast crisis (myBC) of chronic myeloid leukemia (CML, n=5) it was found that the percentage of NBT positive cells was increased by at least 20% as compared to control cultures by rhuGM-CSF in 6/17 cases, by rhuG-CSF in 7/17 cases and by rhuM-CSF in 0/16 cases, representing in responders a mean increase of 267% and 270% in the absolute number of NBT positive cells by rhuGM-CSF and rhuG-CSF, respectively. Morphological examination of cultured cells from responders, as compared to controls, showed decreased blast cell content but generally no evidence of terminal differentiation. The demonstration of Auer rods in NBT positive cells indicates that respiratory burst developed in a leukemic clone. These findings may be of physiological, pathophysiological and clinical relevance.     

A chromosomal profile of polycythemia vera

One hundred four patients with a diagnosis of polycythemia vera and a variable period of follow-up had one or more cytogenetic investigations. Chromosome abnormalities were found in 13% of untreated patients, in 56% of cases treated with radioactive phosphorus (32P) or cytotoxic drugs, and in 85% of patients in which transformation of the disease had occurred. Nonrandom chromosome abnormalities found before treatment included +8, +9, 13q-, 20q-; their prognostic value is little, as they are often associated with longstanding, stable disease. In contrast, 5q- anomaly and the appearance of subclones in patients with an abnormal karyotype were found to be poor prognostic signs, as they are usually coincidental with evolution of the disease to myelofibrosis or leukemia. Chromosomally two patterns of acute leukemia were observed in polycythemia vera patients. The first type resembles de novo acute leukemia, in that the clinical and cytologic characteristics of the disorder are easily defined by FAB criteria and the chromosome changes compatible with the types usually found in those conditions. In the second type, assignment to a FAB morphologic subgroup was more difficult, myelodysplastic changes were often present, and the karyotype showed complex abnormalities frequently involving chromosomes #5 and #7. All these features suggest the occurrence of secondary leukemia.     

Distribution of lymphocyte subsets in a case of angiofollicular lymph node hyperplasia

A series of monoclonal and polyclonal antibodies was used to determine the distribution of lymphocyte subsets in frozen tissue sections of a case of angiofollicular lymph node hyperplasia (ALNH), intermediate type. Primary follicles and mantle zones of secondary follicles consisted of BA1+OKIa1+-C3RTo5+sIgM+sIgD+ lymphocytes. Poorly developed follicular centers reacted with OKIa1, C3RTo5, DRC-1 and anti-IgM but contained no OKT4+Leu-3a+ or Leu-7+ cells. Mantle zones and primary follicles contained more OKT4+Leu-3a+ and less OKT8+ cells than normally observed. The interfollicular area consisted mainly of OKT4+Leu-3a+OKIa1- helper/inducer T-cells, admixed with some OKT8+ suppressor/cytotoxic T-cells and OKIa1+ interdigitating reticulum cells. Polyclonal plasma cells were found both in follicular centers and interfollicular areas. Based on the analogy to the peripheral lymphoid tissue in nude mice and in children with variable thymic dysfunction, it is suggested that the abnormal distribution of immunoregulatory T-cells may be of pathogenetic significance and may account for the morphology of the lymphoid follicles in ALNH.     

5q- anomaly in a patient with disseminated teratoma

A 5q- anomaly associated with other chromosome anomalies was found in the infiltrated bone marrow of a patient with a highly malignant teratoma originally located in the mediastinum. There was no evidence of a second malignancy, and it is likely that the 5q- anomaly was, indeed, associated with the malignant teratoma cells.     

3q−, 3q+ anomaly in malignant proliferations in humans

Anomalies of both No. 3 chromosomes, of the t(3q?; 3q+) type can be observed in human malignancy as reported previously. It is our experience that this anomaly is found predominantly in myeloproliferative disorders, as a rather rare event, though occurring more frequently than similar exchanges between other homologous chromosomes. Previous claims about a relationship between this anomaly and thrombocytosis could not be confirmed, but the features found in a few patients indicate that further research should be undertaken to clarify this point.     

Aorto-septal angulation: a new cause of disorder in left ventricular ejection? (a 2-dimensional echocardiographic study apropos of 66 cases)

Aorto-septal angulation is defined as an acute angled connection between the anterior aortic wall and the interventricular septum. It is quite a common 2D-echo finding. Does it correspond to a simple anatomical curiosity or is it associated with certain well defined diseases? Could it be a cause of obstruction to left ventricular ejection? To try to answer these questions, 66 consecutive cases of aorto-septal angulation were analysed; the echocardiographic and clinical data were correlated. The dynamic features of angulation were studied during the cardiac cycle and the investigations were completed by a phonomecanogramme with pharmacodynamic stress tests. All patients had cardiovascular pathology: aorto-septal angulation was not observed in normal subjects. The dynamic 2D-echo study distinguished two types of angulation with respect to the cardiac cycle: predominantly diastolic angulation tending to correct itself in systole (16 patients: Group CI); the majority of these patients had severe compensated aortic regurgitation; fixed angulation with no significant change between diastole and systole (50 patients: Group C2). This group consisted of patients with ventricular deformation due to coronary artery disease and patients with hypertension associated in some cases with other pathologies. Phonomecanography with pharmacodynamic stress testing in Group C2 revealed the possibility of dynamic obstruction to left ventricular ejection (6 cases) and the apparition of an ejectional systolic murmur (2 cases). Aorto-septal angulation seems to be closely related to hypertension (57% of patients) irrespective of age. Therefore, it should not be classified exclusively as a change observed in the "aging heart" but it may be the direct consequence of an adaptation to systolic strain of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some reasons for the lack of progress in the treatment of acute myelogenous leukemia: a review of three consecutive trials of the treatment of poor prognosis patients

The failure of three consecutive treatment protocols to significantly increase the complete remission rate for poor prognosis newly diagnosed patients with acute myelocytic leukemia led to a detailed investigation of the causes of treatment failure. In the majority of cases treatment failure was attributable to "clinical resistance" to therapy. Upon close examination two types of "clinical resistance" were discernible: the failure of chemotherapy to produce adequate cytotoxic effects ("classical" drug resistance), and treatment failure attributed to the rapid regrowth of leukemia cells subsequent to the substantial killing of leukemia cells by cytotoxic therapy ("biological" resistance). Each form of resistance accounted for one-half of the treatment failures.     

Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.