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activity in AML (Ho and Frei 1971), were introduced along with vincristine and prednisone. 3. The presence of pharmacologic "sanctuaries". While meningeal leukemia has been reported in patients with AML (Pippard et al. 1979; Wolk et al. 1974; Zachariah et al. 1978), it is far less common than in acute lymphocytic leukemia. The central nervous system is the initial site of recurrence in only 10%-15% of relapsing AML patients and is far more often seen in pediatric than in adult age groups (Chard et al. 1978; Pizzo et al. 1976). It was thought conceivable, however, that prolonging survival of patients with AML might yet be associated with an increased incidence of meningeal leukemia (Wolk et al. 1974). The VAPA 10 program did not include treatment directed solely at the central nervous system. Cytosine arabinoside, however, when administered by continuous infusion, has been shown to pass readily through the blood brain barrier, reaching cytotoxic concentrations when administered in doses such as those employed in the early and late intensification plans (Ho and Frei 1971). This approach, especially in the pediatric age grouP, will require re-examination in the future, since 8 of the 16 relapses in patients under age 18 have occurred in the central nervous system. A preliminary analysis of the VAP A 10 experience suggests that age at presentation, sex, or height of the initial white blood count up to 200,000/mm 3 does not have prognostic significance in terms of either remission induction rate or remission duration. The duration of complete remission was further uninfluenced by the number of courses (i.e., whether a seco nd induction treatment was begun on day 14) required to achieve a complete remission. The remission induction rate may be slightly reduced among patients having the acute promyelocytic leukemia subtype (8/15), while the relapse potential seems higher in patients having acute monocytic leukemia (5/10). These data are extremely encouraging and indicate that intensive, sequential combination chemotherapy given to patients with AML who have achieved complete remission can extend the median duration of that remission for 2 years, prolong survival in these individuals for an indefinite period of time, and allow a subsequent period of unmaintained remission in excess of an additional year. The Kaplan-Meier plots (Figs. 3-5) furthermore suggest that a plateau has been achieved among patients who have remained in complete remission for greater than 24 months, making the likelihood of late relapse less and raising the possibility of cure in a significant number of such individuals. The only other therapeutic modality that appears to achieve a similar result for patients with AML is intensive chemotherapy and total body irradiation followed by allogeneic bone marrow transplantation when performed early during the initial remission (Blume et al. 1980 ; Powles et al. 1980; Thomas et al. 1979). This approach, however, is limited to patients who not only achieve a complete remission, but also have a histocompatible sibling. The VAP A 10 experience suggests that AML, even if it is a disease caused by an abnormal bone marrow clone, can be suppressed for extended periods of time by chemotherapy alone in at least 33 % of patients under age 50. It will now be possible to ex amine factors affecting durations of remission and to design specific therapeutic strategies based on these findings. References Armitage JD, Bums CP (1976) Maintenance of remission in adult acute nonlymphoblastic leukemia using intermittent courses of cytosine arabinoside (NSC-63878) and 6-thioguanine (NSC-752). Cancer Treat Rep 60:585-589-Blume KGet al. (1980) Bone marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med 302: 1041-1046 - Bodey GP et al. (1976) Late intensification therapy for acute leukemia in remission: Chemotherapy and immunotherapy. JAMA 235: 1021-1025 - Carey RW et al. (1975) Comparative study of cytosine arabinoside therapy alone and combined with thioguanine, mercaptopurine or daunorubicin in acute myelocytic leukemia. Cancer 36: 1560-1566 - Chard RL et al. (1978) Increased survival in childhood acute nonlymphocytic leukemia after treatment with prednisone, cytosine arabinoside, 6-thioguanine, cyc1ophosphamide, and oncovin (PATCO) combination chemotherapy. Med Pediatr Oncol 4: 263-273 - Clarkson BD et al. (1975) Treatment of acute leukemia in adults. Cancer 36:775-795 - Evans DIK et al. (1975) Treatment of acute myeloid leukemia of childhood with cytosine arabinoside, daunorubicin, prednisone, and mercaptopurine or thioguanine. Cancer 36: 1547-1551 - Gale RPL (1979) Advances in the treatment of acute myeologenous leukemia. N Engl J Med 300: 1189-1199 - Haghbin M et al. (1977) Treatment of acute nonlymphoblastic leukemia in 51
children with a multiple drug protocol. Cancer 49: 1417-1421 - Henderson ES (1969) Treatment of acute leukemia. Semin Hemat 6:271-319 - Ho DHW, Frei E III (1971) Clinical pharmacology of 1-B-D-arabinosylcytosine. Clin Pharmacol Therap 12:944-954 - Moreno H et al. (1977) Cytosine arabinoside and 6-thioguanine in the treatment of childhood acute myeloblastic leukemia. Cancer 40:998-1004 - Peterson BA, Bloomfield CD (1977) Prolonged maintained remission of adult acute nonlymphocytic leukemia. Lancet 2: 158-160 - Pippard MJ et al. (1979) Infiltration of central nervous system in adult acute myeloid leukaemia. Br Med J 1:227-229 - Pizzo PA et al. (1976) Acute myelogenous leukemia in children: A preliminary report of combination chemotherapy. J Pediatr 88: 125-130 - Powles RL et al. (1980) The place of bone marrow transplantation in acute myelogenous leukaemia. Lancet 1: 1047-1050-PreislerHD et al. (1979) Treatment of acute nonlymphocytic leukemia: Use of anthracycline-cytosine arabinoside induction therapy and comparison of two maintenance regimens. Blood 53: 455-464 - Rees JKH, Hayhoe FGJ (1978) DAT (daunorubicin, cytarabine, 6-thioguanine) in acute myeloid leukaemia. Lancet 1: 1360-1361 - Skipper HE (1978) Reasons for success and failure in treatment of mUTine leukemias with drugs now employed in treating human leukemias. In: Cancer Chemotherapy, Volume I. University Microfilms International: Southern Research Institute - Spiers ASD et al. (1977) Prolonged remission maintenance in acute myeloid leukaemia. Br J Med 2:544-547 - Thomas ED et al. (1979) Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Eng J Med 301: 597-599 - Van Hoff DD et al. (1976) 5-azacytide ne : A new anticancer drug with effectiveness in acute myelogenous leukemia. Ann Int Med 82:237-245 - Vaughn WP et al. (1980) Long chemotherapy-free remissions after single-cycle timed sequential chemotherapy for acute myelocytic leukemia. Cancer 45: 859-865 - Weinstein H et al. (1978) Pharmacology of cytosine arabinoside (a-C). Proc Am Assoc Cancer Res 19: 157 - Wolk RW et al. (1974) The incidence of central nervous system leukemia in adults with acute leukemia. Cancer 33:863-869 - Yates JW et al. (1973) Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 57: 485-487 - Zachariah C et al. (1978) Prolonged meningealleukemia: Occurrence during hematologic remission of acute myeloblastic leukemia. JAMA 239: 1423-1424. 52
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Haematology and Blood Transfusion 2
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Dr. Rolf Neth, Universitäts-Kinder
Page 5 and 6:
Participants of the Meeting Aaronso
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Kurth, R, Friedrich-Miescher-Labora
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Wilsede Scholarship Holders (Grante
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Preface Gut ist eine Lehrart, wo ma
Page 13 and 14: Personal and scientific discussion
Page 15 and 16: Acknowledgement We should like to t
Page 17 and 18: Wilsede, June 21 1978 Memorial Trib
Page 19 and 20: limiting benign lymphoproliferative
Page 21 and 22: this most unlikely, however (for re
Page 23 and 24: longer subject to the same control
Page 25 and 26: Bregula U, Wiener F, Harris H (1971
Page 27 and 28: fresh lymph node biopsies from ten
Page 29 and 30: Fig. 3. Binucleate mitosis in an ob
Page 31 and 32: y Fig. 4. Schematic diagram of post
Page 33 and 34: than that among patients with Stage
Page 35 and 36: Tests of binding affinity, agglutin
Page 37 and 38: N Engl J Med 297: 963-968 - Green I
Page 39 and 40: Clinical Aspects
Page 41 and 42: "ring chromosome". "Mar" is marker,
Page 43 and 44: 191 chromosomally abnormal patients
Page 45 and 46: tumors of both African and non-Afri
Page 47 and 48: Haematology and Blood Transfusion V
Page 49 and 50: Retrospective group 26/93 evolved l
Page 53 and 54: Treatment
Page 55 and 56: advantage in terms of duration of f
Page 57 and 58: leukaemia. An analysis of 168 patie
Page 59 and 60: 11. Treatment Program Chemotherapy
Page 61 and 62: efractory congestive heart failure
Page 63: period (Sequence II) was gene rally
Page 67 and 68: DAYS 1 5 10 15 20 25 30 35 , I I I
Page 69 and 70: Biologically Drug Outcome fit" sens
Page 71 and 72: may counterbalance the potential be
Page 73 and 74: Ht (0--0) 50 40 30 20 10 0 Platelet
Page 75 and 76: 10 7 ,-----------------------------
Page 77 and 78: 11. Haematological and Biochemical
Page 79 and 80: 0\ 0\ INTERFERON ... 10 3 rl E "'
Page 83 and 84: ("pre-B" phenotype) has been descri
Page 85 and 86: human bone marrow cells exhibit the
Page 87 and 88: 10 9.,0 MBKCC .. .,4 B prot:oool 1'
Page 89 and 90: demann W, Büehner T, Arlin Z, Gee
Page 91 and 92: -...l 00 a-tLDRENS CAt«:ER S TU>Y
Page 93 and 94: prognostic characteristics under in
Page 95 and 96: significantly higher in HR} (14.5%,
Page 97 and 98: normal or elevated immunoglobulin l
Page 99 and 100: References Andreeff M, Darzynkiewic
Page 101 and 102: R GROUP 1 ( 1970 - 1971 ) 17 PTS. R
Page 103 and 104: Table 3. Influence of initial featu
Page 105 and 106: LIJ (f) a.. < -1 LIJ Q: u. 0 >- I-
Page 109 and 110: me nt indicated that additional the
Page 111 and 112: 42:2123-2134 - Chessells JM, Cornbl
Page 113 and 114: Baum et al. 1979). This study was b
Page 115 and 116:
1. 0 '--'1--" 0.9 e: o .- VI VI E C
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e: o e: 1. 0 ,.--...-- 1'"'\ ......
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In conclusion, we can state that th
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Haematology and Blood Transfnsion V
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INDUCTION VCR + PRED + ASNASE (wk 3
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SCHED.INT 1 MTX • ! Adria MTX •
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~ looh---------ooooc>----o---c>----
Page 129 and 130:
Consoll- Irra .tlon t) .tlon Indu
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Highrisk Standard risk Table 1. Cli
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Cumulo/ive comp/el9 remission 1.0 .
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10° 8 = 6 ö 4 Non T Cell .~ :ö
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Haematology and Blood Transfusion V
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% SURVIVAL 100 ~ ~II 0 80 60 40 - -
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a) Percentage of donor cell mitoses
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Table 5. Results of bone marrow tra
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...... w N Table 7. Clinical result
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agent had to be added and that in t
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C. Chronic Myelogenous Leukemia The
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Patients with a suitable donor rece
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No. Recurrent Leukaemia Other death
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followed by dialysis against isoton
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HS, HL- Heme >_ 40 0 HS I ;:. =====
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knowing at present. These genes may
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esistance to antifolates. In Vitro
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a DNA probe specific for the gene t
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translocation between chromosomes 9
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Table 1. Subdivision of 1827 Myelo-
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NORMAL CELL ®
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some change of the primary type, in
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F. Transformation of Mouse Bone Mar
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were carried out with 3H-MTX in the
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the lysozyme cDNA prepared from ovi
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et al. 1976). The BJAB cellline in
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dalton bands corresponding to light
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1979). The EBV-carrying cell lines
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producer lines (DAUDI and P3HR-1),
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G, Giovanella B, Westman A, Stehlin
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Dc;bt CT + i J.I9 Raji; 1. i .. 100
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c. Discussion During infectious mon
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C. Nonepisomal Viral DNA We have us
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A 260 3.0 A B 1670 70 N2 2.0 c: E .
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vivo. Nature 260:302-306 - Kirk JTO
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Fig. 1. a Polyacrylamide gelelectro
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1979). The lymphocyte subpopulation
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lysin 0 antigens are found, and mix
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Pope JH (1978) Long-term T cell-med
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Charaeteristie Morphologie maturati
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after TPA-induction (Table 3). The
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PA (1978) Reactivity of a rabbit an
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Blood Monocyte. B lood Monocytes 1-
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and nonhistone proteins can serve a
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The findings of the evaluation of s
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Fig. 3. Tumor grawth of L 428 cells
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Cell biological and Immunological A
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consideration. Sanel (1973) obtaine
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endotoxin serum, were used. A parti
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monocytic leukemia cell line in cul
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B. Isolation, Characterization and
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don al hemopathies generally displa
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nitors. Blood Cells 6:595-607 - Min
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\I) ....I ....I IU Jl 200 r 100 90
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their haemopoietic cells' ability t
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normal normal ALL ALL ALL persons p
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64.5 { V)
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References Biermann E, Neth R, Gros
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ehambers, the growth pattern observ
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References Anderssen LC, 10kinen M,
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REH CELL UNE TO CALLb~Ö ~q~ V.M. c
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Page 281 and 282:
the macrophage series in which the
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Table 1. Production of factor depen
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Table 1. Characteristics of the adh
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Fig. 3. A human marrow culture at 6
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300 250 • HYPERPROLIFERATIVE PATT
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Fig. 9. Nonadherent population from
Page 297 and 298:
The cobblestone areas were often no
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L (1976) Induction of colony format
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B. Materials and Methods J. Tissue
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Fig. 2. Ultrastructural appearance
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Table 1. Monoclonal antibody reacti
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al. 1979; Janossy et al. 1979) is e
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to which this is an exact replica o
Page 315 and 316:
inger JL (1976) Distribution of la-
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I region antigens were found to be
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have been reported to be present on
Page 321 and 322:
V. FunctionalAssays Assays for PHA
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Functional studies of UCHT1 separat
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Page 327 and 328:
40 ,...... (5 L.. C o u 30 .9 ~ .~
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with immunohistochemieal methods (L
Page 331 and 332:
Page 333 and 334:
can be dissected by cloning. Utiliz
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Table 1. Origin and marker profile
Page 337 and 338:
Page 339 and 340:
complete identity of gp 100 from no
Page 341 and 342:
Table 1. Reaction of single anti se
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Page 345 and 346:
media. Following 24-h incubation, c
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nonleukemic eells (Greaves 1979). L
Page 349 and 350:
Page 351 and 352:
Fig. 2. Cytocentrifuged smears of b
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Modification of amino-groups of hum
Page 355 and 356:
disturb this balance in the directi
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The majority of human blood lymphoc
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of the EBV infected B cells. Howeve
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and immunoglobulins. J Immunol 120:
Page 363 and 364:
" K 10 • j ~ ALL RNlL AL wtfh les
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tion akuter Leukämiezellen in "spo
Page 367 and 368:
D. Results and Discussion J. Acute
Page 369 and 370:
selectively responsive to different
Page 371 and 372:
Page 373 and 374:
l1J ~ 100 ~ Q. ::) l1J Z 0 ~ z >- .
Page 375 and 376:
Table 2. Growth inhibition of S49 e
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Reverse Infectious ASC/2X1Q6 transc
Page 379 and 380:
Page 381 and 382:
munized animals to 1316 tumor cells
Page 383 and 384:
Page 385 and 386:
Fig. 3. Expression of retroviral gp
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pg70. J Exp Med 143: 151-166 - McGr
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Table 1. Expression of tumor antige
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Virological and Molecularbiological
Page 393 and 394:
Table 1. Oncogenic properties of re
Page 395 and 396:
also Fig. 1). It followed that the
Page 397 and 398:
whether this sequence is related to
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zed in infected cells argue that th
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a specific viral transforming prote
Page 403 and 404:
detect viral RNA as the only charac
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Eisen H (1980) Myeloproliferate vir
Page 407 and 408:
p,60- -34K - 1 2 3 4 Fig. 1. In vit
Page 409 and 410:
.. p - • a'T ... I .t'l Fig. 4. D
Page 411 and 412:
Page 413 and 414:
Fig. 2. Photomicrographs of NY68 in
Page 415 and 416:
DEAE (o(lJmn 'liI GI -2 2 o e s 1
Page 417 and 418:
vity was deterrnined. For endogenou
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pr 180 - - - P 12/15 - A B c D E F
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85,- 66- -27 - -66 40- 27- -1'9 19-
Page 423 and 424:
Page 425 and 426:
= 0.5 o E Q. o ILI 0.4 (J) « ILI .
Page 427 and 428:
Table 1. Oncogenic potential of avi
Page 429 and 430:
100 III GI c: o "8 80 > w
Page 431 and 432:
Expt. No. Infecting virus Proportio
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Haematology and Blood 'fransfusion
Page 435 and 436:
sequences, provided its gag portion
Page 437 and 438:
77:3009-3013 - Hu SSF, Moscoviei C,
Page 439 and 440:
RI 2.2 md and Hind III 2.6 md leuke
Page 441 and 442:
Page 443 and 444:
RELATIONSHIP OF ENDOGENOUS AND EXOG
Page 445 and 446:
E ........ E Cl. U E :::l .... Q) (
Page 447 and 448:
References Astrin S (1978) Endogeno
Page 449 and 450:
the same animal were examined (e.g.
Page 451 and 452:
I) 'IQ a \0 - CL -- Fig. 2. Restrie
Page 453 and 454:
~ ..................... ~ Cell 3' 5
Page 455 and 456:
a :Sa,C! + . ~ 111 i' ( " '~ .J. b
Page 457 and 458:
Table 1 Sampie Tissue TS fragment"
Page 459 and 460:
a b Sac I / rep ._-_.-_ K J nl rep
Page 461 and 462:
Haematology and Blood 'fiansfusion
Page 463 and 464:
Osteopetrosis and osteosarcomas occ
Page 465 and 466:
Lymphoma cellline Table 1. T and B
Page 467 and 468:
Table 2. In vivo growth and oneogen
Page 469 and 470:
Page 471 and 472:
Table 1. Transforming aetivity of c
Page 473 and 474:
Table 3. Transformation aetivity of
Page 475 and 476:
- Shoemaker C, Goff S, Gilboa E, Pa
Page 477 and 478:
indieate a shifting of target eell
Page 479 and 480:
Table 2. Expression of Jl and Sourc
Page 481 and 482:
Page 483 and 484:
~ i ,..1---------,,':::::::::::::::
Page 485 and 486:
fragment of pBR322 DNA, a 3.0-kbp S
Page 487 and 488:
Mak TW (1979) Proc Natl Acad Sci US
Page 489 and 490:
Table 1. Transformation of 3T3 cell
Page 491 and 492:
inserts in the genome of rapidly tr
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pulations, it seemed likely that th
Page 495 and 496:
contains antigens which react with
Page 497 and 498:
Page 499 and 500:
le of reacting in sensitive radioim
Page 501 and 502:
Page 503 and 504:
gic approach. In: Hiatt HH, Watson
Page 505 and 506:
12 Eco R [ Fig. 1. Hybridization pa
Page 507 and 508:
Page 509 and 510:
10 - '1~ )( -~ S:! E A U I o 1 2
Page 511 and 512:
Haematology and Blood 'fransfusion
Page 513 and 514:
cultures. These cells did not conta
Page 515 and 516:
indication of malignant T-cells in
Page 517 and 518:
Fig. 3. Thin-section electron micro
Page 519 and 520:
Table 3. Lack of detectable related
Page 521 and 522:
J. HTLV Was Present in the Primary
Page 523 and 524:
specific signals into nonspecific s
Page 525 and 526:
Table 2. Distribution of HTLV-relat
Page 527 and 528:
u 10 ~ 20 ~ :c 30 a 40 o Fig. 1. Ki
Page 529 and 530:
Page 531 and 532:
SSV TrS-gp labeled effectively with
Page 533 and 534:
Page 535 and 536:
60 HFF/SSV cDNA CELL RNAs: 0 HF/SSV
Page 537 and 538:
Antisera a Table 1. Immunofluoresce
Page 539 and 540:
Haematology and Blood 'ftansfusion
Page 541 and 542:
y competition RIA yielded virtually
Page 543 and 544:
SiS'V' gp70: ANTIGEN, ANTI BODY, IM
Page 545 and 546:
type-C virus p30 antigen in cells f
Page 547 and 548:
c. Results The fractionated whole-b
Page 549 and 550:
induced antibodies as well as exper
Page 551 and 552:
- Fig. la-f. Retravirus particles p
Page 553 and 554:
eplication of infecting murine leuk
Page 555 and 556:
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immunodeficiency, multic10nal lymph
Page 559 and 560:
Bovine leukemia --, proteins of 499
Page 561 and 562:
Human T- cell - -, characterization
Page 563 and 564:
RNA -, of tumor virus 439 Rous sarc
Page 565 and 566:
Haematology andBlood Transfusion Su
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