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PubMed1994

[A patient with adult T cell leukemia in smoldering stage expressing an aberrant phenotype of CD3- and CD4+].

This report is of a patient with adult T cell leukemia (ATL) in the smoldering stage showing expression an aberrant phenotype of CD3-, CD4+ and CD8-. A 71-year-old woman was admitted to our hospital in December 1992, because of skin eruption and persistent low grade fever. Laboratory examination showed a leukocyte count of 7,000/microliter with 29% abnormal lymphocytes. The diagnosis of ATL was made by the detection of serum anti-HTLV-I antibody and the monoclonal integration of HTLV-I proviral DNA in abnormal lymphocytes. ATL cells at diagnosis were CD3+, CD4+ and CD8+. However, one month later ATL cells lacked CD3 and CD8. Three color analysis showed that most of the CD25+ cells were CD3- and CD4+.

Aged↗

PubMed1994

Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection.

We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.

Adult↗

PubMed1994

Variant type of sialyl Lewis X antigen expressed on adult T cell leukemia cells is associated with skin involvement.

Expression of a variant type of sialyl Le(x) antigen defined by 2F3 monoclonal antibody on leukemia cells was studied in 15 adult T cell leukemia (ATL) patients. The expression of 2F3-defined sialyl Le(x) antigen on CD4+CD45+ cells, which is an ATL cell-rich population, was higher in patients with skin involvement (50.1 +/- 23.1% were positive) than in patients without skin involvement (18.1 +/- 12.5%) (P < 0.01). The other surface markers including classical sialyl Le(x) antigen defined by SNH3 or FH6 and LFA-1, VLA-4, CD4, CD25, ICAM-1, Leu8, and HLA-DR did not show a significant difference regardless of skin involvement. In the skin lesion of four patients that we could examine, infiltrating leukemia cells strongly expressed 2F3-defined sialyl Le(x) antigen. In one patient, we could also examine the expression of classical sialyl Le(x) antigen defined by SNH-3 and CSLEX-1, but this was almost negligible. Both skin and lymph node biopsy specimens were examined in two patients. Leukemia cells in the skin strongly expressed 2F3-defined sialyl Le(x) antigen, while its expression was almost negligible on the leukemia cells in the lymph node. These findings suggest that the expression of 2F3-defined sialyl Le(x) antigen on ATL cells is associated with skin involvement of ATL.

Adult↗

PubMed1994

Anti-IL-2 receptor monoclonal antibody (anti-Tac) treatment of T-cell lymphoma.

The abnormal and activated T cells in certain neoplasms of mononuclear cells, select autoimmune disorders, and organ allograft rejection express the IL-2R alpha subunit identified by the anti-Tac monoclonal antibody. In contrast, normal resting cells do not express this inducible receptor. Patients with ATL were treated with different forms of IL-2R-directed therapy to exploit the difference in IL-2R expression between normal and malignant cells. Using the unmodified anti-Tac monoclonal antibody, 7 of 19 patients with ATL treated have undergone a remission (2 cases complete), with no toxicity observed. Unmodified murine monoclonal antibodies are limited by their immunogenicity and poor effector functions. Genetic engineering was used to produce humanized anti-Tac that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1-kappa. This antibody is less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast with the parent antibody, manifests ADCC with human mononuclear cells. To enhance its effector function, anti-Tac was armed with toxins or with alpha- and beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac at the doses used (5, 10, and 15 microCi), 11 of the 17 patients with ATL underwent a partial or sustained a complete remission. Thus, the clinical application of IL-2R-directed therapy represents a new perspective for the treatment of T-cell lymphomas, including HTLV-I-associated ATL.

ADP Ribose Transferases↗

PubMed1993

[Spontaneous remission in adult T-cell leukemia].

Spontaneous remission in a 50-year-old woman with adult T-cell leukemia (ATL) is presented. The patient was referred to our hospital because of generalized lymphadenopathy and the appearance of abnormal lymphocytes with convoluted nuclei in the peripheral blood. She was diagnosed as ATL because of the characteristic morphological ATL cells, cell surface marker analysis and the presence of serum antibody to human T-cell lymphotropic virus type-I (HTLV-I). However during the following weeks before admission, her leukocyte count and ATL cells in the peripheral blood decreased in number even though she received no therapy. After admission, abnormal lymphocytes in the peripheral blood disappeared and lymphadenopathy decreased in size, LDH level was normalized. Spontaneous remission had continued ten months without chemotherapy, but she developed recurrence thereafter and died two years later after onset with progressive disease. Gene analysis study by Southern blot analysis showed monoclonal integration of HTLV-I proviral DNA at the same positions both before regression and after recurrence. In this case, the trigger of spontaneous remission was unclear.

Female↗

PubMed1993

Transcription of the gene for parathyroid hormone-related peptide from the human is activated through a cAMP-dependent pathway by prostaglandin E1 in HTLV-I-infected T cells.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), and hypercalcemia frequently associated with ATL is mediated by parathyroid hormone-related peptide (PTHRP). The present study was undertaken to clarify the role of cAMP second messenger system in the regulation of human PTHRP gene expression in ATL cells, using an HTLV-I-infected T-cell line, MT-2. Forskolin and dibutyryl cAMP (Bt2cAMP) caused a marked and transient increase in the steady-state level of PTHRP mRNA. The effects of these agents were dose-dependent, and the maximal effects were observed at 3 h. Nuclear runoff transcription assay showed that forskolin and Bt2cAMP caused an increase in the transcription rate of the human PTHRP gene. In contrast, the stability of PTHRP mRNA was only modestly increased by these agents. Forskolin and Bt2cAMP also increased the secretion of PTHRP by MT-2 cells, as determined by both a newly established immunoradiometric assay using two antibodies against human PTHRP-(1-34) and PTHRP-(50-83) and a radioimmunoassay using an antibody against human PTHRP-(109-141). Prostaglandin E1 (PGE1) caused a marked stimulation of intracellular cAMP production in MT-2 cells, whereas PGE2 and PGF2 alpha had only modest effects. The ability of these PGs to stimulate cAMP production correlated well with their ability to increase PTHRP mRNA level and the secretion of PTHRP. Indomethacin did not affect the basal level of cAMP production or PTHRP mRNA, suggesting that endogenous PG was not involved in the basal production of cAMP or PTHRP. When PGE1 was given to MT-2 cells together with interleukin 2, which is another stimulator of PTHRP gene expression, PTHRP secretion was synergistically stimulated. These results suggest that the transcription of the human PTHRP gene is enhanced through a cAMP-dependent pathway by PGE1 and that PGE1, as well as interleukin 2, plays an important role in the overexpression of the human PTHRP gene in HTLV-I-infected T cells leading to the development of hypercalcemia in ATL patients.

Alprostadil↗

PubMed1993

[Detection of granulocyte-macrophage colony-stimulating factor activity in the supernatant of the cultured leukemic cells of adult T-cell leukemia with eosinophilia].

An adult T-cell leukemia (ATL) accompanied with eosinophilia is described. A 75-year-old female was admitted to our hospital because of lymphadenopathy. Her leukocyte count was 73,300/microliters, with 35.5% abnormal lymphocytes and 19% eosinophils. A majority of lymphocytes expressed CD4+CD8-. Acute ATL was diagnosed, since anti-HTLV-1 antibody in her serum and monoclonal integration of HTLV-1 proviral DNA in her peripheral mononuclear cells were detected. She was treated with THP-adriamycin, cyclophosphamide (CPA), and vincristine (VCR). Abnormal lymphocyte and eosinophil counts decreased and there was improvement in the lymphadenopathy. However she then complained of lymphadenopathy again. Her leukocyte count rose to 76,300/microliters, with 89% abnormal lymphocytes. Combination therapy with CPA, VCR, and doxorubicin was started and there was a temporal regression in lymphadenopathy, but her lymphadenopathy recurred and she died. The activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected in the supernatant of the cultured ATL cells, although interleukin-3, interleukin-5, and GM-CSF activities were not detected in her serum. It seems likely that the secretion of GM-CSF by ATL cells are responsible for the eosinophilia.

Aged↗

PubMed1996

High expression of ganglioside alpha-2,8-sialyltransferase (GD3 synthase) gene in adult T-cell leukemia cells unrelated to the gene expression of human T-lymphotropic virus type I.

Expression of ganglioside alpha-2,8-sialyltransferase (GD3 synthetase; EC 2.4.99.8) gene and gangliosides in human leukemia cells were analyzed. Flow cytometric analysis of various types of leukemia cells using monoclonal antibodies revealed that GD3 was expressed at a moderate level on adult T-cell leukemia (ATL) cells and weakly on T-cell acute lymphocytic leukemia cells. Accordingly, high levels of GD3 synthase mRNA in ATL and low levels in T-cell acute lymphocytic leukemia were demonstrated by semiquantitative reverse transcription-PCR analysis. High-level expression of the GD3 synthase gene in ATL cells was detected in the uncultured state, and was not changed during short-term culture in vitro. This was in contrast with the rapid up-regulation of GM2/GD2 synthase gene, which was observed within 24 h after start of culture after the emergence of human T-lymphotropic virus type I (HTLV-I) gene expression in cultured normal T lymphocytes with or without HTLV-I p40tax protein, GD3 synthase gene was almost equally expressed, whereas GM2/GD2 synthase gene was much more strongly expressed in the p40tax-positive T cells. These findings indicated that the GD3 synthase gene was highly expressed in ATL cells unrelated to HTLV-I genome expression.

Acute Disease↗

PubMed1996

[Clinical classification of adult T-cell leukemia and its complications].

Since human lymphotropic virus, type 1(HTLV-1) associated adult T-cell leukemia (ATL) has various clinical appearances and courses, it is difficult for the clinician to differentiate acute disease which needs immediate treatment from chronic disease which can be observed with no specific treatment. The Lymphoma Study Group of Japan (1984-87) proposed four clinical subtypes: (1) smoldering type; more than 5% of abnormal T-lymphocytes with less than 4000/microliters of lymphocytes in peripheral blood and few abnormal blood chemistry profiles and ATL infiltration, (2) chronic type; absolute lymphocytosis with T-lymphocytosis of more than 4000/microliters, LDH < 2 times the normal upper limit and no hypercalcemia with possible lymph-node, liver, spleen, skin and lung involvement, (3) lymphoma type; no lymphocytosis with less than 1% of abnormal T-lymphocytes, and histologically-proven lymph-node enlargement, and (4) acute type; the patients not classified into any of the above 3 types. The median survival time (MST) was 6.2 months for acute type, 10.2 months for lymphoma type, and 24.3 months for chronic type; 62.8% of smoldering type was still alive up to 4 years. ATL has a poor prognosis because of life-threatening complications including infections and hypercalcemia. Among infectious complications, cytomegalovirus (CMV) is frequently encountered in autopsy patients. It is important to make an early diagnosis since an anti-CMV agent, ganciclovir is now available for clinical use. It takes 10-14 days to culture CMV in vitro, but now rapid diagnosis can be made by direct immunoperoxidase staining with human monoclonal antibodies against an immediate-early antigen. Another major complication is hypercalcemia. The patients' serum and tumor tissues are found to have parathyroid hormone related protein (PTHrP) associated with hypercalcemia. Serum PTHrP (1-34) is determined by radioimmunoassay and its values seem to be correlated with hypercalcemia and the disease activity. There are still many problems to solve for ATL, but recent advances have been made in clinical subtypes and the above 2 complications.

Adult↗

PubMed1995

Epidemiology of anti-human T-cell leukemia virus type I antibody and characteristics of adult T-cell leukemia in China.

We analyzed the data from seroepidemiologic survey of anti-HTLV-I serum antibody (HTLV-1 Ab) and 16 adult cases of T-cell leukemia (ATL) in China (1984-1994). The results showed that the positive rate of HTLV-I Ab of the population of China was 0.54%, the birth or residence places of HTLV-I carriers and all the patients with ATL were mainly distributed in the coastal provinces and the northeast China, and a small endemic area of HTLV-I and ATl was found in Fujian Province (HTLV-I Ab positive rate, 2.1%). The HTLV-I in China may be transmitted from Japan or originated from China. The clinical characteristics of the cases included onset in adulthood; frequent skin lesions, lymphadenopathy and hepatosplenomegaly; no mediastinal mass; the ATL cells from peripheral blood with polymorphism nuclei and mature T cell immunophenotype HTLV-IAb positive in most of the cases tested (5/8); mostly acute type; with a median survival period of 3.5 months.

Adult↗

PubMed1996

[A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET].

We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-I antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We investigated cerebral blood flow, glucose and amino acid metabolism in this patient using positron emission tomography, and obtained the following three characteristic findings in the lesions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.

Animals↗

PubMed1997

The accumulated experience of the Israeli Advanced Trauma Life Support program.

BACKGROUND: Between January 1990 and May 1995 one faculty in Israel taught Advanced Trauma Life Support (ATLS) courses to 3,700 physicians. Two types of courses were given to three subpopulations. We studied the influence of demographic variables on students' achievements in the course and compared students' achievements as a function of their course type. STUDY DESIGN: This study was conducted as a concurrent longitudinal study. RESULTS: Achievements of 3,700 students were analyzed. The precourse grade, type of course, and their interaction were found to have a significant effect on the postcourse grades. Physicians practicing surgical subspecialties, in general, did better, as did students educated in English-speaking countries. Students who took part in the Combat Trauma Life Support (CTLS) course, which included the entire ATLS course and additional lectures and exercises, also ended with better scores. CONCLUSIONS: Physician's country of origin and clinical subspecialty have a significant effect on the cognitive achievement in the ATLS course provided in Israel. An expanded ATLS course (CTLS), to include additional military trauma topics as well as additional skill station training, can improve the results of the postcourse grades.

Adult↗

PubMed1997

Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells.

It is known that the expression levels of intercellular adhesion molecule-1 (ICAM-1) in adult T cell leukemia(ATL) cells are high, whereas those in T-lymphoid cells are not. In order to investigate the factors that influence the induction of ICAM-1 molecules, Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 (HTLV-1) provirus were done. The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells. However, ILT-mat cells and ATL16T(-) cells, although they were ATL cells, showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression. Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells, respectively, whereas > 10 bands were detected in other ATL cells. These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell, especially the number of integration sites, is one of the factors for induction of ICAM-1 molecules.

Adult↗

PubMed1997

Combat trauma life support training versus the original advanced trauma life support course: the impact of enhanced curriculum on final student scores.

BACKGROUND: Within a military framework, the trauma course student, a young medical officer, is trained to become a trauma team leader and the first provider of medical aid. By adding battlefield medicine-related subjects to the basic Advanced Trauma Life Support (ATLS) course, as well as exercises tailored to the distinctive demands of military medicine, we could develop a special teaching unit: Combat Trauma Life Support (CTLS). The curriculum is basically the complete unchanged ATLS course of the American College of Surgeons enriched with lectures and practicums to fill the gap between the essentially civilian emergency department character of the ATLS course and the military tasks of the medical officer. PURPOSE OF STUDY: To compare the cognitive knowledge achievements of trauma course participants in the Israel Defence Force Medical Corps and to delineate the impact of the course type on students' written test results. DESIGN: A retrospective comparison analysis of pre- and post-course written test scores of 2,614 physicians who had participated in the ATLS and CTLS courses in the Israel Defence Force School of Military Medicine between 1990 and 1993. RESULTS: The analysis indicated that students who undertook the CTLS course achieved statistically better results in written tests (87.9 +/- 8.7 vs. 79.6 +/- 11.4, R2 = 0.33). CONCLUSIONS: We conclude that the CTLS comprehensive curriculum provides an improved training basis for the complex task of army battlefield trauma care support.

Curriculum↗

PubMed1997

Blood flow velocity measurements for carotid stenosis estimation: interobserver variation and interequipment variability.

BACKGROUND: Because of the wide range of recommended threshold values for carotid stenosis graduation we performed a prospective study to determine interobserver and interequipment variability of quantitative blood flow velocity measurements. PATIENTS AND METHODS: We recorded absolute blood flow velocities and velocity ratios in 21 patients with carotid artery stenosis using two colour coded duplex ultrasound systems an ATL Ultramark 9 HDI, and a Hewlett Packard SONOS 2500 system. The ATL system was used for the interobserver variation study, where each patient was examined twice on the same day. The Doppler angle was recorded together with blood flow velocities (peak systolic velocity and mean maximum velocity from the velocity-time-integral both in the stenosis jet and 4-5 cm distally in the cranial portion of the internal carotid artery off poststenotic turbulences). RESULTS: The ATL system generated significantly higher blood flow velocity values as compared with the HP system (218 +/- 156 cm/s vs. 169 +/- 114 cm/s; p < 0.001). The Mean Velocity Ratio (the ratio of intrastenotic Vmean and poststenotic Vmean) was constant with both duplex systems. The HP system yielded 10% (Cl, 7-13%) lower predicted stenosis estimates than the ATL system with Vmax as the stenosis criterion. The stenosis estimates calculated from Mean Velocity Ratio values did not differ significantly. The 95% Cl for predicted diameter reduction between two observer was 13.6% (Vmax) and 15.4% (Mean Velocity Ratio). CONCLUSION: Because of significant interequipment differences of colour coded duplex ultrasound systems we recommend calculation of the Mean Velocity Ratio to avoid interpatient and interequipment variation of absolute flow velocities. According to our interobserver variability study, a change of more than 15% diameter reduction on follow-up examinations indicates disease progression or regression.

Aged↗

PubMed1997

Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53.

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.

Gene Expression Regulation↗

PubMed1997

[Support system for diagnosing hematologic malignancies].

We established a Southern blot hybridization using a DIG-labeled probe to detect monoclonal integration of HTLV-1 proviral genome. DIG was labeled by the PCR method and this probe was as sensitive as the 32P-labeled probe and able to detect only 1.6% of ATL cells. The clinical diagnoses of 44 patients with monoclonal band(s) were all ATL. In contrast, the clinical diagnoses of 39 patients without monoclonal band(s) were diseases other than ATL. We also performed a long PCR of HTLV-1 to characterize the integrated provirus. The method allowed us to find a defective provirus, which was frequently observed in aggressive forms of ATL; 14 of the 18 patients with acute type(78%), 6 of the 9 patients with lymphoma type(67%), and 2 of the 12 patients with chronic type(17%) had the defective provirus. We established a simultaneous PCR for each region of HTLV-1 for further examination of the defective provirus. To detect the monoclonality of IgH gene rearrangement of B-cells, we performed PCR according to the method described. None of 13 patients with T-lymphoproliferative disorders showed a monoclonal band. In contrast, 12 of 13 patients with CLL(92%), 22 of 25 patients with common ALL(88%), 18 of 24 patients with B-lymphoma(75%), and 3 of 3 patients with hairy cell leukemia(100%) showed a monoclonal band. We are now expanding this kind support system for the clinical diagnosis at a molecular biology level in the central laboratory.

Blotting, Southern↗

PubMed1997

[Acute tumor lysis syndrome due to mono-therapy with a corticosteroid in a patient with non-Hodgkin lymphoma].

A 20-year-old man was hospitalised because he nearly suffocated when lying on his back. After bronchoscopy which revealed severe external compression of the airways, suddenly respiratory insufficiency developed. Because a malignant lymphoma was suspected chemotherapy was started, using monotherapy with prednisolone as the risk of acute tumour lysis syndrome (ATLS) is high with polychemotherapy of bulky tumours. Nevertheless ATLS developed, for which haemodialysis had to be applied. The tumour, a T-cell lymphoblastic non-Hodgkin lymphoma with high grade malignancy, was treated successfully with cyclophosphamide, doxorubicin, vincristine en prednisone. ATLS is characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, lactate acidosis and acute renal failure. It can occur in the course of aggressive cytoreductive therapy in rapidly growing lymphoproliferative malignancies with large tumour size, due to massive tumour cel lysis. Corticosteroid monotherapy is a very rare cause of ATLS.

Acute Disease↗