scholarly journals High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia [see comments]

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1305-1310
Author(s):  
AH Sarris ◽  
S Kempin ◽  
E Berman ◽  
J Michaeli ◽  
C Little ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Disseminated Intravascular Coagulation ◽  
De Novo ◽  
Sinus Thrombosis ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Temporal Association ◽  
Remission Induction ◽  
Time Interval ◽  
Intravascular Coagulation

We determined the incidence and complications of disseminated intravascular coagulation (DIC) at presentation and during remission induction of previously untreated adults with acute lymphoblastic leukemia (ALL) or de novo Philadelphia chromosome-positive ALL (PCALL) seen at Memorial Hospital between January 1, 1978 and December 31, 1989. DIC was diagnosed in the presence of (1) low fibrinogen (less than or equal to 160 mg/dL), (2) prolonged prothrombin time (PT) and falling fibrinogen, or (3) prolonged PT and positive fibrin split products (FSP). L-Asparaginase was not used during remission induction. Among adequately screened patients with ALL, DIC was detected in 7 of 58 (12%) before initiation of chemotherapy and in 35 of 45 (78%) during remission induction. DIC was not simply the result of infection because clinical and laboratory signs of infection were absent in 16 patients, whereas only 2 of the 22 febrile patients with DIC had positive cultures. Among the 38 patients with DIC at presentation or during remission induction, serious complications were seen in 13 in temporal association with DIC (pulmonary embolus in one, sagittal sinus thrombosis in three, and serious hemorrhage in nine) and were major factors in the deaths of three patients. Among the 10 patients with thorough screening but no evidence of DIC there was only one hemorrhage during the same time interval. In patients with PCALL, DIC was detected in 9% at presentation and in 80% during remission induction. We conclude that DIC is rare at presentation but common during remission induction of adult ALL and PCALL and may be associated with significant thrombotic and hemorrhagic complications. We suggest daily screening for DIC during the first 14 days of remission induction. The treatment of DIC in ALL and PCALL should be a subject of future clinical studies.

scholarly journals High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia [see comments]

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1305-1310 ◽  
Author(s):  
AH Sarris ◽  
S Kempin ◽  
E Berman ◽  
J Michaeli ◽  
C Little ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Disseminated Intravascular Coagulation ◽  
De Novo ◽  
Sinus Thrombosis ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Temporal Association ◽  
Remission Induction ◽  
Time Interval ◽  
Intravascular Coagulation

Abstract We determined the incidence and complications of disseminated intravascular coagulation (DIC) at presentation and during remission induction of previously untreated adults with acute lymphoblastic leukemia (ALL) or de novo Philadelphia chromosome-positive ALL (PCALL) seen at Memorial Hospital between January 1, 1978 and December 31, 1989. DIC was diagnosed in the presence of (1) low fibrinogen (less than or equal to 160 mg/dL), (2) prolonged prothrombin time (PT) and falling fibrinogen, or (3) prolonged PT and positive fibrin split products (FSP). L-Asparaginase was not used during remission induction. Among adequately screened patients with ALL, DIC was detected in 7 of 58 (12%) before initiation of chemotherapy and in 35 of 45 (78%) during remission induction. DIC was not simply the result of infection because clinical and laboratory signs of infection were absent in 16 patients, whereas only 2 of the 22 febrile patients with DIC had positive cultures. Among the 38 patients with DIC at presentation or during remission induction, serious complications were seen in 13 in temporal association with DIC (pulmonary embolus in one, sagittal sinus thrombosis in three, and serious hemorrhage in nine) and were major factors in the deaths of three patients. Among the 10 patients with thorough screening but no evidence of DIC there was only one hemorrhage during the same time interval. In patients with PCALL, DIC was detected in 9% at presentation and in 80% during remission induction. We conclude that DIC is rare at presentation but common during remission induction of adult ALL and PCALL and may be associated with significant thrombotic and hemorrhagic complications. We suggest daily screening for DIC during the first 14 days of remission induction. The treatment of DIC in ALL and PCALL should be a subject of future clinical studies.

A High Incidence of Disseminated Intravascular Coagulation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia and Its Management

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2500-2500
Author(s):  
Ryota Imanaka ◽  
Taiichi Kyo ◽  
Kayo Toishigawa ◽  
Tetsuro Ochi ◽  
Takeshi Okatani ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Disseminated Intravascular Coagulation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Adult Patients ◽  
P Value ◽  
Intravascular Coagulation ◽  
High Incidence ◽  
Leukocyte Counts

Abstract Introduction Disseminated intravascular coagulation (DIC) occurs about 10% of adult patients with acute lymphoblastic leukemia (ALL) at presentation, and develops in approximately 30-40% of adult patients after starting induction therapy. Although reports of DIC developing with a high frequency in Philadelphia chromosome-positive (Ph+) ALL are scarce, we have experienced many cases of DIC in Ph+ ALL patients. We start chemotherapy and prednisolone (PSL) at the same time after diagnosis of ALL, and give imatinib (IM) at the time it is found to be Ph+. However, we have experienced cases of early death due to severe DIC and tumor lysis syndrome (TLS) when utilizing this approach. Therefore, we have tried mild tumor reduction via initiation of PSL, IM and chemotherapy at different times. We investigated the difference in the incidence of DIC between Ph+ ALL patients and Ph negative (Ph-) ALL patients and discuss the management of DIC and its effect. Patients and methods We examined ALL patients who received their first treatment at our institution between January 2012 and December 2014. We monitored for DIC by twice daily blood testing, and diagnosed DIC according to the diagnostic criteria for DIC of the Japanese Ministry of Health, Labour and Welfare. When DIC developed, the patients were encouraged to rest, and we treated DIC with recombinant human soluble thrombomodulin (rTM) and/or gabexate mesylsate (FOY). To prevent bleeding episodes, platelet (Plt) and fresh frozen plasma transfusion were given to maintain Plt count >50,000/ul and fibrinogen (Fib) level >100 mg/dl. For induction therapy, to avoid rapid development of DIC and TLS, we first administered PSL 60 mg/m2. While confirming a decrease in leukocyte counts and fibrin degradation products (FDP), we started IM followed by chemotherapy (daunorubicin + vincristine + cyclophosphamide + L-asparaginase) in Ph+ ALL patients. We began PSL followed by the same chemotherapy in Ph- ALL patients as well. We used rasburicase to prevent TLS. Results A total of 35 patients with newly diagnosed ALL were examined: 18 patients were Ph+ and 17 were Ph-. The incidence of DIC was 82.3% (14/17) in Ph+ patients and 38.9% (7/18) in Ph- patients. The group with Ph+ showed a significantly higher rate of DIC (p value = 0.015). Duration of the treatment of DIC was 4-14 days (median, 10 days) in Ph+ patients, and 3-10 days (median, 5 days) in Ph- patients. The group with Ph+ also showed significantly longer duration of treatment (p value = 0.02). Twelve Ph+ patients developed DIC (two patients were excluded because of treatment that was different from that described above); five were men and seven were women. Median age was 61 years (range, 34-78 years). Leukocyte counts at the time of diagnosis were 4400-542100 /ul (median 34400 /ul), hemoglobin value was 6.4-15.6 g/dl (median 11.6, g/dl), Plt counts were 6000-262000 /ul (median, 56000 /ul), Fib value was 199-707 mg/dl (median, 299 mg/dl), and FDP value was 3.4-45.7 ug/ml (median, 9.7 ug/ml). DIC occurred at 1-8 days (median, 3 days) from diagnosis. One patient (8%) had DIC at presentation, and the remaining 11 patients (92%) had DIC after the initiation of induction therapy. We started IM at day 3-6 (median, day 5), DIC developed in two patients starting IM, and chemotherapy was started at day 5-10 (median, day 7). Only one patient had slight elevation of FDP, and this value decreased in a progressive fashion in the remaining 11 patients. The maximum FDP value during the treatment of DIC was 32-1162.8 ug/ml (median, 140 ug/ml). We treated DIC with FOY single agent (one patient) or a combination of rTM and FOY (10 patients); all patients showed improvement. The period for improvement of DIC was 4-14 days (median, 8 days), and none of the patients had bleeding or organ damage. Only one patient had TLS, but it immediately improved. In these Ph+ patients, 11/12 patients (92%) achieved complete remission (CR), and one patient had partial remission. Further, 5/5 patients (100%) achieved CR, and none had TLS in the group with Ph-. Conclusion DIC occurred at a high incidence in Ph+ ALL patients. By starting PSL, IM, and chemotherapy at the right time, we can perform induction therapy without generating serious complication due to DIC. Disclosures No relevant conflicts of interest to declare.

scholarly journals P190BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature

2021 ◽  
pp. 1040-1050
Author(s):  
Samah Kohla ◽  
Sarah EL Kourashy ◽  
Zafar Nawaz ◽  
Reda Youssef ◽  
Ahmad Al-Sabbagh ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Rare Case ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Cytogenetic Abnormality ◽  
Rare Case Report ◽  
Philadelphia Chromosome Positive

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 <i>BCR-ABL1</i>) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1858-1858 ◽  
Author(s):  
Daniel J. DeAngelo ◽  
Lewis B. Silverman ◽  
Stephen Couban ◽  
Suzanne Dahlberg ◽  
Philip C. Amrein ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Demographic Data ◽  
Philadelphia Chromosome ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Childhood All

Abstract Background: In children with ALL, current chemotherapy regimens produce an event-free survival (EFS) of greater than 80%. Adults with ALL have a much poorer prognosis, with EFS rates of 30–40%. Recent retrospective studies suggest that young adult patients may have superior outcomes when treated on more intensive pediatric regimens, but prospective studies are lacking. A phase II trial was performed in an effort to determine if an intensive pediatric regimen can be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based upon the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00–01. Patients with newly diagnosed ALL were enrolled and received intensive multiagent remission induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, high-dose asparaginase, and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of 3 week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of high-dose asparaginase that was individually dosed in order to maintain asparagine depletion. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 71 patients have been enrolled to date. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18–50 with de novo ALL; this amendment excluded 4 patients from the analysis. Two patients were enrolled but never received therapy. Demographic data are available for 61 evaluable patients. The median age was 28 years, (range, 18–50), 65% were male, 75% had B-lineage phenotype, and 13% were Philadelphia chromosome positive. In the 54 patients for whom response data was available, the 4 week CR rate was 82%. Among the patients who had the opportunity to complete Intensification therapy, asparaginase data was available for 23 patients, 18 (78%) of whom completed all 30 weeks. One death occurred during induction therapy from sepsis. Four patients developed grade 3 pancreatitis and one patient died of grade 5 pancreatitis. The latter case represented the only remission death on study. There were two cases of osteonecrosis, 10 cases of thrombosis/embolism and 12 cases of neutropenic infection that occurred during the post-remission period. At the median follow-up time of 18.4 months, the estimated EFS is 75% (95%CI: 61–89%) and the overall survival is 79% (95%CI: 65–93%). Conclusions: These results suggest that administration of a dose intensified pediatric-like strategy is feasible. Although the high EFS rate requires longer follow up and larger confirmatory studies, such intensive treatment of young adults with ALL could represent a major therapeutic advance.

Augmented Berlin-Frankfurt-Muenster Based Therapy For Young Adults With Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1400-1400 ◽  
Author(s):  
Michael E. Rytting ◽  
Deborah A. Thomas ◽  
Susan O'Brien ◽  
Kurt Schroeder ◽  
Rebecca Garris ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Philadelphia Chromosome ◽  
Significant Difference ◽  
Grade Iii

Abstract Pediatric-based therapy of acute lymphoblastic leukemia (ALL) has been proposed as superior treatment for teen-agers and young adults with ALL. Several trials report improved survival rates in young adult ALL patients (pts) when treated with pediatric-based regimens. Augmented Berlin-Frankfurt-Muenster (ABFM) treatment is effective treatment for ALL in adolescents up to age 21. In an attempt to improve cure rates in AYA pts with ALL, we administered ABFM therapy to pts age 12 to 40 in a prospective, single institution trial. Results were then retrospectively compared to the HYPER CVAD regimen, the historical adult ALL regimen used at our institution. 85 pts with de novo Philadelphia chromosome negative ALL have completed at least 6 months of therapy. There are 69 (81%) pts with pre-B ALL and 16 (18%) pts with T-cell ALL/lymphoma. The age range is 13-39 with a median of 21. The median WBC at diagnosis is WBC=14 thousand/microliter (range 0.4-494). 80/85 (94%) pts entered remission (<5% blasts on day 29 marrow morphology). 1 patient died during induction. 61(72%) pts attained remission at day 15 of induction. 29 (22%) did not have morphological remission by day 15 of induction. At the end of induction, 46(58%) pts were minimal residual disease (MRD) negative by flow cytometry (<0.01% blasts). 25(31%) were positive for MRD and 6(7%) were not available or equivocal. By approximately day 84 of treatment, 55(69%) pts were negative for MRD and 13(16%) were positive or suspicious. Toxicities encountered include severe allergy to PEG-asparaginase in 17 (20%) pts, thrombosis in 18 (21%), hyperbilirubinemia grade III-IV in 31 (36%), elevated ALT grade III-IV in 28 (33%), hypofibrinogen grade III-IV in 30 (35%), pancreatitis in 9(11%), and avascular necrosis in 9 (11%). Grade III-IV hepatic toxicity is frequent but resolves within two weeks in almost all pts. For the entire cohort, the estimated 3 year overall survival (OS) is 75% and 3 year complete remission duration (CRD) is 71%. In univariate analysis, negative MRD at day 29 was associated with improved OS and day 84 negative MRD was associated with improved CRD. The presenting WBC was associated with OS and CRD. On multivariate analysis, only WBC over 50k/microliter maintained significance for OS and CRD. In comparing ABFM to HYPER CVAD, there is no significant difference in OS or CRD between the two regimens (fig. 1 and 2). This lack of difference in OS and CRD persists when patients are stratified for age > or </= 21 years, for presenting WBC over 50 thousand, and for MRD at the end of induction. In our hands, pediatric based therapy has significant though tolerable toxicity. Outcomes in AYA pts are similar but not superior to results obtained with historical ALL therapy. Disclosures: No relevant conflicts of interest to declare.

Experience With BFM 95 Pediatric Regimen In Adult ACUTE Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5015-5015 ◽  
Author(s):  
Hakan Goker ◽  
Eylem Eliacik ◽  
Ayse Isik ◽  
Ibrahim C. Haznedaroglu ◽  
Nilgun Sayinalp ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Adult Acute Lymphoblastic Leukemia ◽  
High Doses ◽  
Dose Reductions

Abstract As treatment of adult acute lymphoblastic leukemia (ALL) is unsatisfactory compared to pediatric disease, there is ongoing interest in the treatment of adult ALL with pediatric regimens. In this context we started to use BFM 95 pediatric regimen (Blood 2008;111:4477) in relapsed adult ALL cases in April 2010 and extended this approach to newly diagnosed non-Burkitt and and non-Ph+ ALL cases aged < 30. Nineteen cases (15 male, 4 female; 11 de novo, 8 relapsed) have been treated during this period in Hacettepe University Med. Ctr. Hematology dept., Ankara, Turkey. Median (range) follow-up durations after BFM 95 regimen and after remission attainment were 4.3 months (1.6-31) and 4.25 (0.4-21.4). Median age was 22 (17-27) in de novo cases and 24 (20-46) in relapsed patients. Three out of 8 relapsed cases had relapsed after allogeneic stem cell transplantation (AlloSCT). Complete remission ratio was 18/19 (95%). One relapsed patient died during induction due to sepsis. The BFM 95 regimen primarily served as a remission induction protocol in relapsed cases. None of these cases completed the treatment protocol. They generally underwent AlloSCT (6 cases) or donor lymphocyte infusion (1 case) shortly after complete remission. Therefore these cases were censored at the time of transplantation in survival analyses. Two out of 11 newly diagnosed patients completed the protocol. In two other cases the treatment was stopped after 2 and 4 consolidation courses for AlloSCT. One de novo patient died in remission. The remaining six de novo cases are still on treatment. Sixteen patients were still alive by the time of last follow-up. Two deaths (during induction and consolidation) and 1 relapse were observed by this time. Median (95% confidence interval) estimated overall and disease-free survival durations were 31 months (not calculable) and 19.4 months (2.6-36.2), respectively. Grade 3-4 non-infectious toxicities were observed only in 5 (%26) patients during treatment. Liver dysfunction, pancreatitis, acute renal failure, and mucositis were occasionally observed. These significant toxicities were due to high doses of methotrexate (5 g/m2) and L-asparaginase (25 000/m2) which were used during early periods of this study. After adequate dose reductions these toxicities were not observed subsequently. Dose reduction for high dose dexamethasone (60 mg/m2) and CMV surveillance were also deemed necessary after one case of fatal CMV reactivation was observed during IIA consolidation protocol. In conclusion, BFM 95 regimen seems to be highly efficacious with a 95% CR rate in young adults. In order to reduce excess toxicities, appropriate dose reductions are necessary for high doses of methotrexate, L-asparaginase and dexamethasone which are applied during various steps of this regimen. However, longer follow-up and more patients and controlled studies are needed in order to reach firm conclusions. Disclosures: No relevant conflicts of interest to declare.

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