scholarly journals The myth of the second remission of acute leukemia in the adult

Blood ◽  
2013 ◽  
Vol 121 (7) ◽  
pp. 1077-1082 ◽  
Author(s):  
Stephen J. Forman ◽  
Jacob M. Rowe
Keyword(s):  
Acute Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Myelogenous Leukemia ◽  
Curative Therapy ◽  
Successful Transplantation ◽  
Acute Myelogenous ◽  
First Remission ◽  
First Relapse

Abstract Although the majority of adult patients with both acute lymphoblastic leukemia and acute myelogenous leukemia achieve remission with upfront chemotherapy, many patients still suffer relapse. Often, the strategy is proposed of treating patients with relapsed leukemia into a second remission (CR2) and then proceeding to allogeneic transplantation as the definitive curative approach. However, the long-term outcomes of such a strategy are poor: the 5-year overall survival from first relapse for patients with acute leukemia is only approximately 10%. This Perspective highlights the fact that most patients do not achieve CR2 and therefore never really have an opportunity for a potential curative therapy. Although patients who undergo transplantation after relapse may be cured, those who do not achieve CR2 are rarely candidates for transplantation; therefore, the overall outcome for patients who relapse is dismal. There is therefore an urgent need not only for more effective upfront therapy to prevent relapse, but also for the development of therapies that can serve as effective bridging treatments between relapse and transplantation. We suggest that more optimal use of minimal residual disease detection during first remission may also improve the chances for successful transplantation therapy via earlier reinduction therapy, allowing transplantation before overt relapse.

scholarly journals Immunophenotypic study of acute leukemia by flow cytometry at BPKMCH.

2013 ◽  
Vol 3 (5) ◽  
pp. 345-350
Author(s):  
S Shrestha ◽  
J Shrestha ◽  
CB Pun ◽  
T Pathak ◽  
S Bastola ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Acute Myelogenous Leukemia ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Examination ◽  
Myelogenous Leukemia ◽  
Female Ratio ◽  
Flow Cytometric ◽  
Male Female Ratio ◽  
Acute Myelogenous

Background: Immunophenotyping of acute leukemia is one of the most important clinical applications of fl ow cytometry. The aim of this study was to determine the immunophenotyping profi le of acute leukemia, by means of a fl ow cytometric method, using monoclonal antibodies all marked with a fl uorochrome, in four colour systems to assess their distribution according to type of leukemia (lymphoid B or T / myeloid). Materials and Methods: We retrospectively collected data of immunophenotyping from 52 acute leukemia patients at the department of pathology in B.P. Koirala Memorial Cancer Hospital from January 2010 to December 2011. Diagnosis was based on peripheral blood and bone marrow examination for morphology, cytochemistry and immunophenotypic studies. Results: Out of total 52 cases of acute leukemia diagnosed by fl ow cytometry over a two year period, there were 31 cases (59.6 %) of acute lymphoblastic leukemia, 20 cases (38.4 %) of acute myelogenous leukemia and one case (1.9 %) of bi-phenotypic acute leukemia. Leukemia was diagnosed among adults in 44.2 % whereas among children with age less than or equal to 15 years in 55.7 %. Thirty eight (73%) were male and 14 (27 %) were female with a male: female ratio of 2.7:1. For acute myelogenous leukemia, it was found that M0 (5.0 %), M1 (20%), M2 (60%), M3 (15%), M4 (5.0 %) were detected. CD13 and CD33 were the most useful markers in the diagnosis of acute myelogenous leukemia. The most common subtype was AML-M2. Of the 31 cases with acute lymphoblastic leukemia, 20 cases (64.5 %) were identifi ed as B-ALL and 11 cases (35.5%) as T-ALL. Aside from cytoplasmic CD3 (cCD3) and CD7 were the most sensitive antigens present in all cases of T-ALL. All cases of B-ALL showed expression of pan B-cell markers CD19 and CD22, but 15 (75 %) of 20 cases expressed CD10. Conclusion: Flow cytometric immunophenotyping was found to be especially useful in the correct identifi cation and diagnosis of acute myeloid or lymphoblastic leukemia and its subtypes. In combination with French-American-British (FAB) morphology and immunophenotyping, we were able to diagnose and classify all patients with acute leukemia in this study. Journal of Pathology of Nepal (2013) Vol. 3, No.1, Issue 5, 345-350 DOI: http://dx.doi.org/10.3126/jpn.v3i5.7856

scholarly journals Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2920-2928 ◽  
Author(s):  
DS Snyder ◽  
NJ Chao ◽  
MD Amylon ◽  
J Taguchi ◽  
GD Long ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Graft Versus Host ◽  
Acute Myelogenous ◽  
Total Body ◽  
First Complete Remission

Abstract Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

Decreased Expression of Telomere Length Regulating Factors TRF1, and Tankyrase 1 in Patients with Adult Acute Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4421-4421
Author(s):  
Wenbin Qian ◽  
Xiudi Yang ◽  
Weilai Xu
Keyword(s):  
Acute Leukemia ◽  
Telomere Length ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Telomere Elongation ◽  
Binding Factor ◽  
Telomere Function ◽  
Acute Myelogenous ◽  
Tankyrase 1

Abstract Telomeric repeat binding factor 1 (TRF1) and Tankyrase 1 (a human telomeric poly(ADP-ribose) polymerase) may play key roles in the maintenance of telomere function. TRF1 negatively regulates telomere elongation, while Tankyrase 1 acts as positive regulator of telomere length. In this study, we examined the expressions of TRF1 and Tankyrase 1 in 46 samples from patients with acute leukemia at diagnosis by quantitative reverse transcription real-time polymerase chain reaction and then analyzed the relation with the expression of protooncogene c-myc. TRF1 mRNAs were significantly down-regulated in patients with acute leukemia compared to controls. On the other hand, the mononuclear cells (MNCs) of patient with acute myelogenous leukemia (AML) expressed TRF1 at higher levels than that of patient with acute lymphoblastic leukemia (ALL) (p<0.01) or myelodysplastic syndrome (MDS). Compared to the patients with CD 34 negative AML, patients with CD34 positive AML expressed lower levels of TFR1 (p<0.01). The expression levels of Tankyrase 1 mRNA progressively decreased in patients with MDS, AML and ALL, although it was not significant. Moreover, there was a significantly correlation between the expression of TRF1 mRNA and Tankyrase 1 mRNA in AML cells (r = 0.394, p<0.01). Expression of c-myc mRNA was found gradually reduced in patients with AML, ALL and MDS. Otherwise, the expression level of TRF1 significantly correlated with those of c-myc in patients with AML(r=0.381, p=0.02) and CD34 positive AML (r=0.814, p<0.01). These results suggest that TRF1 gene expression in acute leukemia is down-regulation, and higher expression of TRF1 mRNA may be a reason for shorter telomere in some AML cells. There is dysfunction of TRF1 expression in the CD34 positive subset of AML. The patients with lower expression of TRF1 may have a poor prognostic.

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

1990 ◽  
Vol 8 (11) ◽  
pp. 1907-1912 ◽  
Author(s):  
R Ohno ◽  
K Okada ◽  
T Masaoka ◽  
A Kuramoto ◽  
T Arima ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Phase Ii ◽  
Early Phase ◽  
Topoisomerase I ◽  
Phase Ii Study ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Cross Resistance ◽  
Treatment Schedule ◽  
Acute Myelogenous

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia.

1987 ◽  
Vol 5 (3) ◽  
pp. 371-375 ◽  
Author(s):  
Z A Arlin ◽  
T Ahmed ◽  
A Mittelman ◽  
E Feldman ◽  
R Mehta ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Effective Therapy ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Once Daily ◽  
Blastic Phase ◽  
High Dose Cytarabine ◽  
Acute Myelogenous

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.

Bone Marrow Transplantation for Children Less Than 2 Years of Age With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3546-3556
Author(s):  
Ann E. Woolfrey ◽  
Ted A. Gooley ◽  
Eric L. Sievers ◽  
Laurie A. Milner ◽  
Robert G. Andrews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Acute Myelogenous Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
First Remission ◽  
First Relapse ◽  
Disease Free

We analyzed results of 40 infants less than 2 years of age who received bone marrow transplants (BMT) between May 1974 and January 1995 for treatment of acute myelogenous leukemia (AML; N = 34) or myelodysplastic syndrome (MDS; N = 6) to determine outcome and survival performance. Among the AML patients, 13 were in first remission, 9 were in untreated first relapse or second remission, and 12 were in refractory relapse. Patients were conditioned with cyclophosphamide in combination with either total body irradiation (TBI; N = 29) or busulfan (N = 11). Source of stem cells included 6 autologous donors, 15 HLA genotypically identical siblings, 14 haploidentical family members, and 5 unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was methotrexate (MTX) for 17, MTX plus cyclosporine (CSP) for 14, or CSP plus prednisone for 3. Incidence of severe (grade 3-4) regimen-related toxicity was 10% and transplant-related mortality was 10%. Acute GVHD (grades II-III) occurred in 39% of allogeneic patients, and chronic GVHD developed in 40%. Relapse, the most significant problem for patients in this study, occurred in 1 MDS patient and 23 AML patients and was the cause of death for 19 patients. The 2-year probabilities of relapse are 46%, 67%, and 92%, respectively, for patients transplanted in first remission, untreated first relapse or second remission, and relapse. One MDS and 8 AML patients received second marrow transplants for treatment of relapse, and 5 of these survive disease-free for more than 1.5 years. All 6 MDS patients and 11 of 34 AML patients survive more than 1.5 years later. The 5-year probabilities of survival and disease-free survival are 54% and 38% for patients transplanted in first remission and 33% and 22% for untreated first relapse or second remission. None of the patients transplanted with refractory relapse survive disease-free. Outcome was significantly associated with phase of disease at transplantation and pretransplant diagnosis of extramedullary disease. Long-term sequelae included growth failure and hormonal deficiencies. Survival performance was a median of 100% (80% to 100%) and neurologic development for all survivors was appropriate for age. This study indicates that infants with AML have similar outcome after BMT compared with older children and that BMT should be performed in first remission whenever possible. In addition, allogeneic BMT provides effective therapy for the majority of infants with MDS.

Phase I Study of Temozolomide in Relapsed/Refractory Acute Leukemia

2002 ◽  
Vol 20 (15) ◽  
pp. 3249-3253 ◽  
Author(s):  
Karen Seiter ◽  
Delong Liu ◽  
Thomas Loughran ◽  
Ahmad Siddiqui ◽  
Paul Baskind ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Maximum Tolerated Dose ◽  
Myelogenous Leukemia ◽  
Platelet Recovery ◽  
Acute Myelogenous ◽  
Dose Limiting Toxicity

PURPOSE: To determine the dose-limiting toxicity and maximum-tolerated dose of temozolomide in patients with acute leukemia. PATIENTS AND METHODS: Twenty patients (16 with acute myelogenous leukemia, two with acute lymphoblastic leukemia, and two with chronic myelogenous leukemia in blastic phase) received 43 cycles of temozolomide. Patients began treatment at two different dose levels: 200 mg/m2/d for 7 days or 200 mg/m2/d for 9 days. RESULTS: Prolonged aplasia was the dose-limiting toxicity, and the maximum-tolerated dose was 7 days of temozolomide. Overall treatment was well tolerated: hospitalization was required in only nine of 43 courses, and there were no treatment-related deaths. Two patients obtained a complete response, and two others met criteria for complete response except for platelet recovery. Overall, nine of 20 patients had a significant decrease in bone marrow blasts after temozolomide treatment. CONCLUSION: Temozolomide was well tolerated and had significant antileukemic activity when administered as a single agent. Further studies of temozolomide in hematologic malignancies are indicated.

Tuberculous Skeletal Muscle Involvement in Acute Leukemia: Report on Two Cases

1997 ◽  
Vol 83 (2) ◽  
pp. 618-620 ◽  
Author(s):  
Auro del Giglio ◽  
Hélio Pinczowski ◽  
Gileno Portugal ◽  
Olavo Feher
Keyword(s):  
Skeletal Muscle ◽  
Acute Leukemia ◽  
Clinical Course ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Imaging Studies ◽  
Muscle Involvement ◽  
Acute Myelogenous ◽  
Bacteria And Fungi ◽  
Skeletal Muscle Involvement

Bacterial infection of skeletal muscle (pyomyositis) is usually followed by abscess formation. The most commonly isolated pathogen is Staphylococcus aureus. Tuberculosis rarely affects patients with acute leukemia. The authors report on 2 patients, one with acute myelogenous leukemia and the other with acute lymphoblastic leukemia whose clinical course was complicated by tuberculous skeletal muscle abscesses. In both instances, musculoskeletal pain was accompanied by evidence of muscle abscesses by imaging studies of the painful areas. Therefore, in patients with acute leukemia and evidence of muscle abscesses with initial cultures negative for bacteria and fungi, one should include tuberculosis in the differential diagnosis.

Frequency, Risk Factors, and Outcomes of Vancomycin-Resistant Enterococcus Colonization and Infection in Patients with Newly Diagnosed Acute Leukemia: Different Patterns in Patients with Acute Myelogenous and Acute Lymphoblastic Leukemia

2015 ◽  
Vol 36 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Clyde D. Ford ◽  
Bert K. Lopansri ◽  
Souha Haydoura ◽  
Greg Snow ◽  
Kristin K. Dascomb ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Acute Myelogenous Leukemia ◽  
Molecular Typing ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Newly Diagnosed ◽  
Acute Myelogenous ◽  
Vancomycin Resistant

OBJECTIVETo determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia.DESIGNRetrospective clinical study with VRE molecular strain typing.SETTINGA regional referral center for acute leukemia.PATIENTSTwo hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012.METHODSAll patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System.RESULTSThe rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality.CONCLUSIONSVRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.Infect Control Hosp Epidemiol 2015;36(1): 47–53

scholarly journals Classifying acute leukemia by immunophenotyping: a combined FAB- immunologic classification of AML

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1355-1362 ◽  
Author(s):  
PB Neame ◽  
P Soamboonsrup ◽  
GP Browman ◽  
RM Meyer ◽  
A Benger ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Gold Standard ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Fab Classification ◽  
Acute Myelogenous ◽  
French American British

Abstract A panel of commercially available monoclonal antibodies and five heteroantisera were used to distinguish and subtype 138 cases of acute leukemia (AL). The immunophenotype was compared with the French- American-British (FAB) classification obtained on the cases. The immunophenotype discriminated acute myelogenous leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognized cases not distinguished by cytochemistry (22% of cases), mixed lineage phenotypes (13% of cases), and cases with separate populations of lymphoblasts and myeloblasts (one case). Using the immunologic panel and derived criteria to subtype AML, correspondence of the immunophenotype to the FAB subtypes M1, M2, M4, and M5 was possible in greater than 80% of cases. A combined classification of the immunophenotype and FAB morphology/cytochemistry was devised for AML subtyping. It is recommended that immunophenotyping should be done at least in all cases with negative orinconclusive cytochemistry. At present, we suggest that until a “gold standard” for identifying leukemic subtypes is developed, the best method for typing acute leukemia is by using a combination of morphology, cytochemistry and immunophenotyping.

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