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From www.bloodjournal.org by guest on April 28, 2017. For personal use only. Serum Lactic Dehydrogenase Marked (LDH) Elevations Serum total lactic dehydrogenase leukemia. mean range while that of patients range was i26-684 (26.8%) with of serum with acute the i9 case levels between L the crisis during and are a range LDH values ANLL and levels different are cell damage, A relationship LDH levels workers, in Elevated tissues LDH as well both of and statistically of ALL. were levels as in lU/liter. that in individual exists animal encountered serum of tumors. tumor not 0.001 ). the in 42 patients with cate that LDH cases of acute levels are moderately leukemia, irrespective the but studied acute Serum until LDH Nineteen Burkitt’s leukemia ANLL (20 et crisis, for the ALL (mean admission started. Blood. to the In four Vol. 56, hospital patients and non-Hodgkin’s and multiple ALL, lymphoma, myeloma (iron-deficiency idiopathic and thrombophlebitis) liver damage cases of acute ries (ALL and cytochemistry, markers and levels and in 1980 leukemia lupus The (CLL), nonmalignant erythematosusaplastic signs anemia, of hemolysis and series. in the peroxidase, sudan paranuclear acid diagnosed ifcells esterases and phosphatase. black, and A proportion surface ALL of markers: red ALL FC while surface some black, or were C3 0. In for positive 0. sudan red negative were red sudan inhibition, oil were oil receptor, stains fluoride PAS, cases cell (PAS), and and 0, catego- microscopy by Schiff if cells for either oil main cytochemical without PAS. for cases phosphatase, esterases, positive two of light acid and as phosphatase, were following acid classified negative difficult The with esterase, into basis more periodic esterases were classified on the for ANLL was peroxidase, paranuclear or acid examined for receptors, the surface are method determined. were primarily and peroxidase, Hospital were I 7-77 yr). Hodgkin’s with with this ultrastructure.3233 cases following leukemia ANLL), performed: general, METHODS isoenzymes LL group 34 in of age of Leukemia nonspecific chemotherapy from range malignancies: systemic I2 6 of them (mean patients I). Cases excluded Classtfication AN yr purpura-ITP, (Table were chloroacetate before anemia, had leuke- I I males, lymphatic 30 thrombocytopenic black, the and with patients The 26 yr), chronic (MM), acute CML, 2 females). with As-D on with (7 males, with monoblastic leukemia; 9 patients 53 patients in many cell type. in all cases No. 3 (September), of 2 patients 23 promyelocytic examined included and from 24-62 were done sera group mdi- was with levels number patients with yr (mean results determination 2 patients AML, I I -70 The to the with CML leukemia. according 42 was levels determined and the LDH LDH the including and LDH LDH in ALL, yr), material the Department and Hebrew day of Address of ofHematology. was of Hematology, Hadassah University-Hadassah Medical University School. Jeru- Israel. Submitted The serum with group serum elevated of their assayed had with were 46 control salem, al.3’ while in serum elevated 8 females), I patient blastic All with Assay Morgensten crisis. differences (1 1 males, In addition, total AND were myeloid now, and in blastic crisis of chronic but not in any of the patients with leukemia (ANLL). These results levels In 1 5 of chronic lymphoblastic The Patients lU/liter). with the in 6 cases lU/liter. 1038 correlated were patients patients and From LDH (ANLL). and 900 + 3 patients were levels leukemia. SLE, In with to correlate suggest that markedly elevated serum more indicative of ALL than ANLL. Serum over The lU/liter, Material disorder 30 However, markedly elevated levels were recorded the majority of patients with acute Iymphoblastic Enzyme levels chronic 1 13 leukemia markedly levels ± 313 lymphoma of 1669 as ALL. that LDH with disorders. and with had regarded It appears Patient yr between of solid elevated but shown we have a non-Hodgkin’s mass,2029 been MATERIALS had value 3 patients not patients. lU/liter In addition. of these was females). in neoplastic patients with In Recently, leukemia (ALL) myeloid leukemia, acute nonlymphatic patients One but 210 (1 1 .3%) (mean lU/liter. 9 patients nonlymphoblastic patients lU/liter mia, tumors.’’9 Burkitt’s lymphoma,22#{176} elevated in many patients, and In acute of these 900 to LDH levels have frequently been observed.22’ addition, there appears to be a good correlation levels have of leukemia. in subsequent there does not appear to be a good correlation increased LDH levels and specific types tumors. In animal and human leukemias, elevated the type (p < significant and and and are the particularly levels are activity above prednisone. (LDH) systems, human disease None leukemia. lymphoproliferative 402 ± was In 6 of the of 402-3582 serum LDH levels may be between neoplasia and has been reported by many epithelial lymphoma, serum LDH lU/liter. acute other relapse. cell tissue or elevated. increased 500 with and ± 74 lU/liter. 308 of 970-1940 DEHYDROGENASE many variety had to vincristine suggestive remission ACTIC above (ALL) patients lymphoma ± 146 lU/liter). were had clinically was Polliack lymphoma non-Hodgkin’s disorders serum with Leukemia: Leukemia Aaron in 42 patients of 413 levels ALL. and and examined 53 value leukemia with Kornberg were and in Hodgkin’s (mean in blastic ALL levels crisis, nonmalignant LDH responded leukemia blasts levels with (78.9%) (CML) second in blastic lU/liter ANLL. patients in acute LDH lymphoblastic leukemia (LDH) 6 of them in Acute in Lymphoblastic By Abraham myeloid Levels © /980 February reprint 20. 1980; requests Hadassah by Grune accepted to Aaron University & Stratton. April Polliack. Hospital, 23. 1980. M.D., Jerusalem, Department Israel. Inc. 0006-4971/80/5603-01Y33$0I.0O/0 351 From www.bloodjournal.org by guest on April 28, 2017. For personal use only. 352 KORNBERG Table 1 . Range and Mean Values o f Serum LDH in 1 25 Patients Leukemia. Lymphoma. and Nonmalignant Range of Serum LDH Levels (lU/Liter) Mean ± SD Serum LDH levels (lU/Liter) 19 402-3.582 1.669 ± ANLL 23 126-684 413 ± Hodin’sdisease 15 226-898 402 ± Non-Hodgkin’slymphoma 23 1.038 146 160-590 313 ± 210 113 CLL 9 254-444 335 ± 69 MM 6 184-488 317 ± 114 30 180-491 308 ± 74 Iron disorders deficiency 5 Thrombophiebitis 8 Aplastic 4 anemia SIE 6 ITP 7 immunoglobulin, sera. In some were performed analysis anemia was E-rosettes, cases, and T-antigen transmission to done assist and using scanning in definition according of to Student’s the t anti-I-cell electron cell anti- microscopy type. Statistical test. The serum LDH and I. The normal Hadassah This is where the number range of LDH nizedinTable The levels from of levels, 1. the range the cases groups are patients and the in each mean values of acute shown in group, the malignant disonHodgkin’s and nona range of LDH levels from ± 226 the ane summa- lU/liter MM liter. of in was total serum LDH Hospital is 100-500 the nonmalignant 180-491 lU/liter in the lU/liter. disorders, (mean value ‘a to 898 3000 LDH (mean levels lU/liter). value were 210 lU/liter), In all and 413-146). above the patients In 6 ANLL 500 (78.9%) the values only 4 patients the Isoenzymes and in all were levels lU/liter above were In 6 500 with less than 500 IU/ LDH was 126-684 patients, (543-684), no patient had levels above 900 lU/liter. The levels in ALL was 402-3582 lU/liter (mean 1661 ± 1038 lU/liter). In 15 of the 19 ALL blastic crisis, while type but responded :D 402 the levels were the range ofserum three of the patients metamorphosis, the 970-1940 lU/liter). A 2000 (mean (588-898 and CLL, In ANLL, lU/liter range University reflected in all control was 308 ± 74 lU/liter). Among dens, sena from patients with Hodgkin’s lymphoma displayed 160-590 (mean 313 ± 1 13 lU/liter), respectively. of the above 38 patients, LDH levels were above RESULTS leukemia POLLIACK Disorders ALL Nonmalignant :i: Acute No. of Patients Clinical Diagnosis Fig. With AND but range of value of patients 900 lU/liter, while below 500 lU/liter. in In with CML, all in acute blastic LDH levels were elevated (range One ofthese cases had a lymphothe to second was vincnistine were determined these cases both in only isoenzymes undifferentiated and prednisone. in 4 ALL patients, 2 and 3 were - found to be elevated; however, isoenzyme 3 was more markedly elevated than isoenzyme 2 in these patients. a 1000 There is no statistically serum LDH levels among leukemia and the various - ;t:- ;T z< 1 - LSCL MM. 2,o t, I 02 O. Z Il 0 1-i 0 z the absolute number ofcirculating ALL blasts and the serum LDH levels (Fig. 2). This phenomenon may be explained by the possibility that elevated serum LDH levels may relate more to total leukemic cell mass than to the numbers of circulating blasts. However, in individual Fig. disorders. 1 . Serum LDH level in > in the ANLL 0.05). However, the differences in LDH levels between the ALL patients and all the other groups were statistically significant (p < 0.001). On initial admission, no correlation existed between ODD DO ;: significant difference the patients with control groups (p neoplastic and non-neoplastic found relapse. patients during This with cytotoxic is cleanly ALL, good treatment, demonstrated correlation was remission, and in Fig. 3 and 4, From www.bloodjournal.org by guest on April 28, 2017. For personal use only. LDH IN ACUTE 353 LEUKEMIA 0 ACUTE LYMPHOSLASTIC . ACUTE NON 11000 LEUKEMIA LYMPHOBLASTIC LEUKEMIA 2.10 0-c WBC x-x LYMPHOBLASTS ..-. LDH ‘10000 00 0 9000 8000 0 E 0 “_‘% C..) 0 iv 4 6000 -A 0 I 0 0 5000 .-J 0 4000 0 0 0 S 0 S S 7 #{149} S. 102 10 NO.OF 2000 S 1O 1O 1000 serum LDH levels and the blast leukemia and nonlymphoblastic elevation 10 20 of Serum vitamin B,2 in I 2 of the 15 serum LDH. No 20 30 10 20 I BUARY 2800 action 30 10 20 intermediate and during a shift in the the development LDH isoenzymes the granulocytic mainly isoenzymes is the and early predominant and 1-3, MONTHS of fetal and adult In hematopoietic LDH-l-3, while in pnoenythroMaturing lymphocytic but at the blast cells series stage, LDH-5. In normal I and 2 predominate, have as yet not been with tissue damage similar and with respect both cell types human plasma, of contain LDH-I and -2 are decreased, resulting in a predominance LDH-3. Mature peripheral blood lymphocytes mainly leukemia. lympho- of embryonic pattern occurs. isoenzyme nonmoblasts.303435 granulocytes are quite LDH isoenzyme content, 30 frac- hybrid forms of association of the of LDH-l and 5. is determined by the activity of controlling LDH-l and LDH-5. isoenzymes are found in various 800 IOCTOBER Fig. 3. A 24-yr-old woman with acute lymphoblastic Correlation of serum LDH level, the number of circulating blasts. and the WBC count. the blasts 400 20 while 1200 LDH-5 10 genes, 1600 -4 :i: ISEPTEMSER of two Accordingly, the isoenzyme content cells of the same type is different. tissues, enythrocytes contain mainly 2000 U 30 leukemia. lympho- Lactic dehydrogenase occurs in different cell systems in the form of five isoenzymes, LDH-1-5.34 The production of LDH- I and LDH-5 is controlled by tissues, organs, 2400 E 30 I DISCUSSION Their concentration the two alleles Different LDH 3200 30 10 20 I AUGUST 10 I JANUARY tions (LDH-2-4) are considered LDH-I and LDH-5, formed by peptides making up the tetnamens 3600 20 30 Fig. 4. A 1 6-yr-old woman with acute lymphoblastic Correlation of serum LDH level, the number of circulating blasts, and the WBC count. the 4000 JULY 10 20 cases showed megaloblastic changes on vitamin B,2/folic acid deficiency. (Vitamin B,2 recorded from 360 pg/ml to 4000 pg/ml; folic acid 160-320 ng/ml.) 10 30 I DECEMBER NOVEMBER MONTHS obtained in two patients. acid levels were available with 0 BLASTS/mm3 Fig. 2. Correlation between counts in acute lymphoblastic leukemia. patients S S5 S from data and folic 3000 S S of and to their contain isoenzymes but the sources of this activity clearly established. In conditions and rapid cell turnover, such as From www.bloodjournal.org by guest on April 28, 2017. For personal use only. 354 KORNBERG malignant neoplasia, the isoenzyme damaged organ In the moderately the serum distribution and cells. present study, serum elevated in 6 of ANLL and lymphoma. LDH usually may rise, reflects total LDH 23 patients and that of the levels (26%) were with increased activity in isolated in the serum of patients transplantable lymphatic Bunkitt’s lymphoma, LDH with ALL leukemia. the serum contrast to the above data lymphoblasts and the findings as a rough indicator more, when these elevated lymphoma. LDH between acute those obtained for other statistically groups, significant. they Among the were CML enzyme levels were elevated in one lymphoblastic crisis and in another case tiated type prednisone. are highly tic type. crisis In our who responded opinion, marked suggestive of acute Recently, in the present Our results et al.22 Sactor the raised LDH levels towards obtained 26 who Angeletti patterns and PU, of protein muscle Bierman serum lactic patients and in mice. 2. BR, Moore BW: in extracts Res Hill by Stuart have shown Chromatographic with lymphomas the and clinical status Cancer drogenase of I961 glutamic-oxaloacetic 4. BR, Hill during Levi disease. Cancer Hill FL: Serum transaminase masses JH: 6. KM. Cancer Elevation lactic component in neoplastic cancer 689, patients. J HI: Serum Proc Soc lactic Exp Biol 7. Hsieh KM. Mao activity after 19:700-764, 8. White 17. 91:626-630, 9. Suntzeff lactic Res K, dehydrogenase Meister normal A: ED, and Res Lactic J Nail Huggins levels dehydro- Cancer Res Comparative of serum transplanted and induced 1956 dehydrogenase Cancer C: cancers. Scoch F: Glutathione of tissues 18:682-686, of pyridine of experimental mammary 12. Starkweather WH, with Wroblewski activities Cancer tissues. 1 1 . Rees glycolysis, lactic tumors. EV: in mice 16:237-239, C, Sugiura tumors. 10. V, Cowdry activity Cancer Manso planted K: Serum of transplanted of rodents Steroid with trans- of certain 10:1263-1271, influences nucleotide-linked Cancer Res HK: Some tumors LP: Serum cancer and on respiration, dehydrogenases 20:963-97 observation 1 , I 960 on the by of malignant found in in cell Biochim heterogeneity Ann NY Biophys of lactic Acad Weinhouse Res I 2:44-49, dehy- 94:877-889, Metabolism citric acid of cycle in 1952 II. diseases. Sci 5: of the enzymes. other 18. Glycolytic J NatI F, their enzymes Cancer Inst in 21 :671- of3O 22. AR: system Lactic J Res IC: Burkitt’s from in activity Lactic in dehydrogenase PM, 1964 Berard CW, lymphoma: 58:314-321, 1975 and leukemic Gral- A clinicopa- Alpha-glycerophosphate cells and 1961 24:389-399, Banks J Med isoen- plasma 1955 Hall Am and dehydrogenase NO, GP, of hematopoietic Stuart of abnorpatients. dehydrogenase tissues 94:912-932, American cases. B, Dick Lactic Cancer Canellos VT: of cancer 90:210-213, Kaplan JC, study Sactor Med tissues. DeVita drogenase transport iS: RD. Arseneau thologic F, Ladue neoplastic HR. KF: Sci Biol significance in normal Acad Exp Goldman 20. Gregory NY The serum 1958 distribution Ann III. in the 21:685-696, ProcSoc in human enzymes. enzymes Wroblewski blood. nick Serum Inst 20:1408-1412, 1950 shift accompanied in the levels tissue. of enzymes Cancer LP: and 21. 1958 activity Inst reductase MA, Wroblewski zymes 19. KM. dehydrogenase tumors. Sasamanonth Spirtes of glycolytic Cancer 1959 Hsieh lactic 55, excision a glycoly- different of the II. A survey diseasestates. genase reflects increased neoplastic tissues. tumors. with malities dehydrogenase Med In 1958 Natl 1957 states. in in human CE, White 16. in and Significance tissue. patients 1954 Blumenthal disease IS. measurements I 956 and Wenner transplanted and 23: 1 1 2- 1 1 7, 1963 dehydrogenase 18:307-313, in various dehydrogenase with Res of serum 14:513-515, Serum Inst Hsieh C: lactic correlations therapy. Res NatlCancer and 14. Res ES: activity neoplastic Francis clear. 1962 Vessell of 1957 CO. activity of human 62:440-442, I 3. leukemias. LDH metabolism encountered dehydrogenase Acta E: Correlation is not NCES 1960 L, Emory LDH lactate of rhabdomyosarcoma 20:1229-1234, Reinhardt activity cancer, of tumor levels enzymes dehydrogenase with Brindley 5. V. Cancer HR. 12:660-667, 3. Suntzeff leukemias malignant distinction neoplasms and the markedly elevated levels patients with ALL may reflect basic differences proliferation and turnover in these disorders. REFERE I. cellular anaerobic serum series. are similar to those et al.,2’ and other223 with the sis in the cytoplasm of malignant cells a high turnover rate.2237 The variations have megakanyonature were this it is of interest to record that other demonstrated increased LDH levels in transplanted induced munine myeloid leukemias.2729 Increased of lymphoblas- chronic of levels in 47 of and in all 36 also recorded in 86% of patients from their study, and this respect, authors have primary and to vincnistine and elevations of LDH been recorded in rare patients with acute blastic leukemia,36 but no cases of this studied to be patient with of undiffenen- leukemia markedly found patients, with with are and LDH levels tumor mass.2#{176}In study, Bierman et al.2 reported elevated 54 patients with lymphatic leukemia patients with myeloid leukemia. They levels However, and in animals In patients LDH levels 900 lU/liter. In ALL, LDH levels were markedly elevated. In 15 of 19 patients (79%), the levels were above 900 lU/liter, and in some cases, could be used of the total tumor mass. Furtherlevels in ALL were compared to POLLIACK and frequently elevated above 700 IU/ml, were found to correlate well with the in 6 of 38 patients (16%) with malignant None of these patients had levels above AND mice. lactic dehy- Cancer Res 1960 J, Simpson iS, in acute Mann leukemia. JR: Br Intracellular J Haematol hydrogen 19:739-748, I 970 23. Chrispens CG: Serum lactic dehydrogenase levels in mice From www.bloodjournal.org by guest on April 28, 2017. For personal use only. LDH IN ACUTE during the tumors. J NatI 24. serum 355 LEUKEMIA development of Cancer Friend C, in mice with Inst autochonous and 30:361-366, Wroblewski F: chemically induced 3 1 . Morgenstern 1962 Lactic transplantable dehydrogenase leukemia. activity Science of 32. JM: 25. Hill BR, Jordan RI: leukemia Serum of mice. lactic Proc Am dehydrogenase activity Assoc Res Cancer in 2: 1 17, I 956 mice Hill RB, with 27. 28. genase ofthe 29. 30. Stratton, C, J NatI enzyme. myeloid Cancer Nishio Res K, Jacobson lactic dehydrogenase of enzyme JW: erythroblasts leukemia. 17:144-147, Glucose of on avian in 1957 and plasma II. On 23:344-348, 1963 KB, VK, Jenkins to course activity viral 33. acute 1974, Baikie p 524 A: Leukemia HR. Galton G, enzymes, Klein AG, B: Automatied determination 13:149-161, of lactic 1965 Catovsky D, Sultan Ann Intern Med leukemia. McKenzie A scanning granulocytic Am S. Gee electron I, J Med C, Bennett 87:740-753, N, Dc study monoblastic 59:308-314, WH, Lampen microscopic myelomonocytic Starkweather mice the lactic site 35. dehydro- Harven E, of 34 cases and of histiocytic 1975 Spencer of hemopoietic bead Upton with myeloid of disease. Cancer AC: Rabinowitz isoenzymes of production HH, cells. Studies on 36. Ottolander I. blastic leukemia Haematol 23:340- (ed 3). New York, Grune & lactate neoplastic Dietz Schoch Blood M, A: Malic leukemic 29:182-195, GJD, Velde (acute 42:9-20, Field and Blood leukemia. Res Y, of normal columns. 37. G, Biochem A, BD: dehydrogenases 1963 Gunz Anal ofacute Polliack 34. leuke- Kessler I977 leukemia. lactate R, HK: 28:860-872, The lactate 1966 1959 K: Studies in level Res Baard 23:261-275, Hishio dehydrogenase Cancer GS, and Inst KB, with lactic leukemia. Cancer in mice Serum Beaudreau myeloblasts Jacobson Relation RI: transplantable by plasma 343, Jordan Becker utilization mias. Gralnick Flor NAD-coupled Classification Clarkson 26. of dehydrogenase. 124:173-174, I956 transplanted 5, determination and leukocytes lactic dehydrogenase separated on glass 1967 iT, Brederoo myelofibrosis), P. et al: a report of three Megakaryocases. Br J 1979 Block elevations proliferative among JB, Levin R, RaIl patients with disorders. Am DP: acute J Med Significance leukemia 40:528-547, of blood and 1966 other From www.bloodjournal.org by guest on April 28, 2017. For personal use only. 1980 56: 351-355 Serum lactic dehydrogenase (LDH) levels in acute leukemia: marked elevations in lymphoblastic leukemia A Kornberg and A Polliack Updated information and services can be found at: http://www.bloodjournal.org/content/56/3/351.full.html Articles on similar topics can be found in the following Blood collections Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.