scholarly journals Chemotherapy of the blastic phase of chronic granulocytic leukemia: hypodiploidy and response to therapy

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1003-1009 ◽  
Author(s):  
GP Canellos ◽  
VT DeVita ◽  
J Whang-Peng ◽  
BA Chabner ◽  
PS Schein ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cytosine Arabinoside ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Blast Cell ◽  
Response To Therapy ◽  
Chronic Granulocytic Leukemia ◽  
Blastic Phase ◽  
Response To Chemotherapy ◽  
Granulocytic Leukemia

Abstract Thirty-two patients in the blastic phase of Philadelphia chromosome- positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine-- prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine-- prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.

scholarly journals Chemotherapy of the blastic phase of chronic granulocytic leukemia: hypodiploidy and response to therapy

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1003-1009
Author(s):  
GP Canellos ◽  
VT DeVita ◽  
J Whang-Peng ◽  
BA Chabner ◽  
PS Schein ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cytosine Arabinoside ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Blast Cell ◽  
Response To Therapy ◽  
Chronic Granulocytic Leukemia ◽  
Blastic Phase ◽  
Response To Chemotherapy ◽  
Granulocytic Leukemia

Thirty-two patients in the blastic phase of Philadelphia chromosome- positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine-- prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine-- prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.

scholarly journals Hematologic and Cytogenetic Remission of Blastic Transformation in Chronic Granulocytic Leukemia

Blood ◽  
1971 ◽  
Vol 38 (6) ◽  
pp. 671-679 ◽  
Author(s):  
GEORGE P. CANELLOS ◽  
VINCENT T. DEVITA ◽  
JACQUELINE WHANG-PENG ◽  
PAUL P. CARBONE
Keyword(s):  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Chronic Granulocytic Leukemia ◽  
Blastic Transformation ◽  
Blastic Phase ◽  
Granulocytic Leukemia ◽  
Subsequent Relapse

Abstract Thirty patients in the blastic phase of chronic granulocytic leukemia were treated with a combination of vincristine, 2.0 mg/sq m weekly, and prednisone, 60 mg/sq m orally each day. Remission was achieved in nine patients (30%), six of whom had a complete remission, and three had a good partial remission. The survival of responding patients was significantly improved over the nonresponders. Cytogenetic studies were performed on all patients in the chronic phase of the disease, and in 28 during the blastic phase. All were Philadelphia chromosome-positive throughout their course. Aneuploidy developed in 68% of the patients entering the blastic phase. Complete hematologic remission was accompanied by disappearance of aneuploid blast cell lines in the five patients in which they were detected, with return of the chromosomal constitution to that which characterized the chronic phase of their disease. Hypodiploidy in blastic transformation of CGL appeared to predict for a favorable response to vincristine and prednisone. Subsequent relapse of the disease in previously remitted patients was associated with further degrees of aneuploidy, suggesting clonal evolution of a resistant cell line.

Long Survival in Philadelphia-Chromosome-Positive Acute Leukemia

1986 ◽  
Vol 72 (3) ◽  
pp. 313-316
Author(s):  
Indira Sahdev ◽  
Ram S. Verma ◽  
Harvey Dosik
Keyword(s):  
Acute Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Chronic Granulocytic Leukemia ◽  
Long Survival ◽  
Ph Chromosome ◽  
Granulocytic Leukemia ◽  
Philadelphia Chromosome Positive

A case of Philadelphia (Ph')-chromosome-positive acute leukemia (AL) is presented who went into remission with disappearance of the Ph1 chromosome and later on developed the chronic phase of chronic granulocytic leukemia (CGL) with reappearance of the Ph1 chromosome. The patient is alive 6+ years following the diagnosis. The entity of Ph1-positive AL is discussed. It is suggested that the patients with Ph1-positive AL who develop CGL have a better prognosis than previously described.

scholarly journals Treatment of refractory splenomegaly in myeloproliferative disease by splenic artery infusion

Blood ◽  
1979 ◽  
Vol 53 (5) ◽  
pp. 1014-1017
Author(s):  
GP Canellos ◽  
SB Sutliffe ◽  
VT DeVita ◽  
TA Lister
Keyword(s):  
Cytosine Arabinoside ◽  
Splenic Artery ◽  
Symptomatic Relief ◽  
Spleen Size ◽  
Myeloproliferative Disease ◽  
Massive Splenomegaly ◽  
Chronic Granulocytic Leukemia ◽  
Previous Therapy ◽  
Blastic Phase ◽  
Granulocytic Leukemia

Five patients in the blastic phase of chronic granulocytic leukemia with massive splenomegaly were treated by intraarterial splenic artery infusion of cytosine arabinoside. All patients had massive splenomegaly associated with pain and/or hypersplenism and were refractory to previous therapy. All 5 patients demonstrated responses to treatment, with reduction in spleen size as well as symptomatic relief. Systemic toxicity was minimal in 4 of the 5 patients.

scholarly journals Dibromomannitol in the treatment of chronic granulocytic leukemia: a prospective randomized comparison with busulfan

Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 197-203
Author(s):  
GP Canellos ◽  
RC Young ◽  
PE Neiman ◽  
VT Jr DeVita
Keyword(s):  
Disease Control ◽  
Leukocyte Count ◽  
Skin Pigmentation ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Remission Induction ◽  
Chronic Granulocytic Leukemia ◽  
Duration Of Disease ◽  
Granulocytic Leukemia ◽  
Primary Agent

Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.

scholarly journals Prognostic significance of terminal transferase and adenosine deaminase in acute and chronic myeloid leukemia

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 685-692 ◽  
Author(s):  
U Bertazzoni ◽  
E Brusamolino ◽  
P Isernia ◽  
AI Scovassi ◽  
S Torsello ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Adenosine Deaminase ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Response To Therapy ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Stable Phase ◽  
Blastic Phase ◽  
Blast Cells

Abstract We have analyzed the distribution and prognostic significance of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) in connection with conventional cytology, cytogenetics, response to therapy, and survival. The study population consisted of 78 patients with AML, 44 patients with Ph1 + CML in chronic phase, and 35 adult patients with Ph1 + CML in blastic phase, among which 5 cases presented as Ph1 + acute leukemia. Nine percent of the AML cases were positive for TdT and were characterized by a high percentage of blast cells in bone marrow, myeloid features by cytochemistry and absence of the Philadelphia chromosome. The median ADA values of the TdT+ AML cases were several times higher than those obtained for the TdT- cases. The survival calculated for the two groups of AML cases subdivided according to ADA levels was significantly longer (p less than 0.025) for the patients with low levels of ADA (less than 250 U/10(8) cells). In chronic phase of CML, TdT was absent and ADA values were increased over normal controls only in cases with early signs of transformation. In blastic phase, 31% of the 35 cases were positive for TdT, and ADA values were significantly higher (p less than 0.001) in TdT+ than TdT- cases. The survival calculated from the onset of transformation was significantly longer for the TdT+ acute phase (10.4 mo) compared to the TdT- patients (4.8 mo; p less than 0.025). Four cases presenting as Ph1 + acute leukemia were TdT+ and had elevated levels of ADA; 3 of them responded to ALL therapy, reverting to a stable phase of CML.

scholarly journals Chronic granulocytic leukemia: cytogenetic conversion of the bone marrow with cycle-specific chemotherapy

Blood ◽  
1977 ◽  
Vol 50 (1) ◽  
pp. 107-113 ◽  
Author(s):  
RV Smalley ◽  
J Vogel ◽  
CM Jr Huguley ◽  
D Miller
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Drug Treatment ◽  
Cytosine Arabinoside ◽  
Fatal Outcome ◽  
The Other ◽  
Nausea And Vomiting ◽  
Chronic Granulocytic Leukemia ◽  
Negative State ◽  
Granulocytic Leukemia

Sixteen patients with Ph1-positive chronic granulocytic leukemic (CGL) were entered on a pulsing chemotherapy program consisting of cytosine arabinoside 100 mg/sq m/day X 5 and thioguanine 100 mq/sq m/day X 5 every 21 days in an attempt to convert the Ph1-positive marrow to a Ph1- negative state and thereby achieve a complete remission. Twelve patients had an adequate trail of drug treatment, and ten of these had adequate chromosome examinations. There were two “conversions,” one of which was maintained for 5+ mo, while the other was transient. The program was unacceptable, however, to most patients due to intolerable nausea and vomiting. Thus a prospective chemotherapeutic attempt to convert a Ph1-positive marrow without splenectomy has induced a conversion in two of ten patients. Other regimens which might induce less nausea and vomiting and a higher rate of conversions should be sought in future attempts to alter the invariably fatal outcome of CGL.

scholarly journals Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia

Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 11-16 ◽  
Author(s):  
JH Schwartz ◽  
GP Cannellos
Keyword(s):  
Alkylating Agents ◽  
Chronic Phase ◽  
Blast Cell ◽  
Blastic Crisis ◽  
Rapid Reduction ◽  
Chronic Granulocytic Leukemia ◽  
Peripheral Leukocyte ◽  
Duration Of Disease ◽  
Granulocytic Leukemia ◽  
Definite Role

The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL.

scholarly journals Prognostic significance of terminal transferase and adenosine deaminase in acute and chronic myeloid leukemia

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 685-692
Author(s):  
U Bertazzoni ◽  
E Brusamolino ◽  
P Isernia ◽  
AI Scovassi ◽  
S Torsello ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Adenosine Deaminase ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Response To Therapy ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Stable Phase ◽  
Blastic Phase ◽  
Blast Cells

We have analyzed the distribution and prognostic significance of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) in connection with conventional cytology, cytogenetics, response to therapy, and survival. The study population consisted of 78 patients with AML, 44 patients with Ph1 + CML in chronic phase, and 35 adult patients with Ph1 + CML in blastic phase, among which 5 cases presented as Ph1 + acute leukemia. Nine percent of the AML cases were positive for TdT and were characterized by a high percentage of blast cells in bone marrow, myeloid features by cytochemistry and absence of the Philadelphia chromosome. The median ADA values of the TdT+ AML cases were several times higher than those obtained for the TdT- cases. The survival calculated for the two groups of AML cases subdivided according to ADA levels was significantly longer (p less than 0.025) for the patients with low levels of ADA (less than 250 U/10(8) cells). In chronic phase of CML, TdT was absent and ADA values were increased over normal controls only in cases with early signs of transformation. In blastic phase, 31% of the 35 cases were positive for TdT, and ADA values were significantly higher (p less than 0.001) in TdT+ than TdT- cases. The survival calculated from the onset of transformation was significantly longer for the TdT+ acute phase (10.4 mo) compared to the TdT- patients (4.8 mo; p less than 0.025). Four cases presenting as Ph1 + acute leukemia were TdT+ and had elevated levels of ADA; 3 of them responded to ALL therapy, reverting to a stable phase of CML.

scholarly journals Chronic Granulocytic Leukemia and the Philadelphia Chromosome

Blood ◽  
1963 ◽  
Vol 21 (2) ◽  
pp. 183-196 ◽  
Author(s):  
P. H. FITZGERALD ◽  
ANGELA ADAMS ◽  
FREDERICK W. GUNZ
Keyword(s):  
Complete Remission ◽  
Acute Phase ◽  
Chromosome Abnormality ◽  
Philadelphia Chromosome ◽  
The Other ◽  
Direct Examination ◽  
Chronic Granulocytic Leukemia ◽  
The One ◽  
Granulocytic Leukemia ◽  
Very High

Abstract Twelve patients with chronic granulocytic leukemia were examined for the presence of the Ph1 chromosome abnormality at various stages of their disease. The abnormality was demonstrated either in the blood or marrow of all patients. Patients in relapse showed very high numbers of Ph1-positive mitoses in both blood and marrow; those in remission showed relatively few or no positives in the blood but sizeable numbers in the marrow. There was a positive correlation between the degrees of abnormality of blood and marrow on the one hand, and the percentage of Ph1-positive mitoses on the other. Direct examination of the marrow for the demonstration of the Ph1 appeared of particular value in the acute phase of chronic granulocytic leukemia. It seemed likely that therapy depressed the number of abnormal (Ph1-positive) mitoses. There was, however, no evidence that these ever disappeared from the marrow, even in complete remission. The findings presented and those in the literature did not make it possible to decide in what way the Ph1 chromosome abnormality is related to the onset of leukemia.

Sign in / Sign up

Export Citation Format

Share Document