scholarly journals Acute Promyelocytic Leukemia: 37 Years Long Ongoing Survival in a de novo Patient with Metal-Based Ayurvedic Treatment

2020 ◽  
Vol 06 (03) ◽  
pp. 147-148
Author(s):  
Balendu Prakash ◽  
Shikha Prakash ◽  
Sneha Tiwari
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
Bone Marrow Aspiration ◽  
Promyelocytic Leukemia ◽  
New Delhi ◽  
Medical Centers ◽  
All Trans Retinoic Acid ◽  
Established Line ◽  
Ayurvedic Treatment

AbstractAcute promyelocytic leukemia (APML) is a subtype of acute myeloid leukemia. The condition is clinically marked by anemia, fatigue, weakness, frequent infections, and fever associated with easy bleeding and coagulopathy. The diagnosis is made through bone marrow aspiration exhibiting increased promyelocytes and test for PML-RARα fusion gene. There has been remarkable progress in the treatment of APML in the past few decades with the induction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). This has also brought down mortality and relapse rates considerably. Similarly, nearly 90% patients are able to live disease free for about 10 years. However, there are certain hindrances to these treatments majorly due to side effects, relapses, and limited periods of remission associated with ATRA and ATO. Here, a freshly diagnosed case of APML is being reported. The patient was diagnosed in leading medical centers of Aligarh and New Delhi and only treated with blood transfusions in the absence of an established line of treatment in 1982. The patient has completed 37 years long survival without any sign of the disease and any adverse effect. This approach could be considered as an add-on medical therapy for APML.

scholarly journals PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1313 ◽  
Author(s):  
Marta Sobas ◽  
Maria Carme Talarn-Forcadell ◽  
David Martínez-Cuadrón ◽  
Lourdes Escoda ◽  
María J. García-Pérez ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
High Relapse Rate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Shed Light

It has been suggested that 1–2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

scholarly journals RARα1/RARα2-PML mRNA Expression in Acute Promyelocytic Leukemia Cells: A Molecular and Laboratory-Clinical Correlative Study

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 306-312 ◽  
Author(s):  
Yun-Ping Li ◽  
Janet Andersen ◽  
Arthur Zelent ◽  
Sreenivas Rao ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Promyelocytic Leukemia ◽  
Gene Promoters ◽  
All Trans Retinoic Acid ◽  
The Difference ◽  
Therapy Protocol ◽  
Expression Frequency

Abstract In addition to the major fusion gene PML-RARα, the t(15; 17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RARα-PML. To determine the scope of RARα-containing mRNA expression in APL cells, we tested PML-RARα–positive APL cells for the presence of mRNAs initiated from two distinct RARα gene promoters, α1 and α2. From the normal allele, both RARα1 and RARα2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RARα1-PML mRNA was expressed in 77% and RARα2-PML mRNA in 28% of cases (N = 98). RARα2-PML mRNA was not observed in the absence of RARα1-PML mRNA. There was no association between RARα1-PML or RARα2-PML mRNA expression and the type of PML-RARα mRNA formed by either 5′ or 3′ breaksites in the PML gene. RARα1-PML mRNAs and RARα2-PML mRNAs from 5′ PML breaksite cases coded for full-length RARα-PML proteins but RARα2-PML mRNAs from 3′ PML breaksite cases encoded a truncated RARα2 peptide. RARα1/α2-PML mRNA expression was not associated with differences in APL cell sensitivity to all-trans retinoic acid(tRA)-induced differentiation in vitro or in clinical outcome after tRA or chemotherapy induction therapy (protocol E2491). Our analysis indicated that RARα1/α2-PML mRNA expression markedly differs from normal RARα1/α2 mRNA expression, that the difference in RARα1-PML and RARα2-PML mRNA expression frequency is primarily related to the genomic separation of the RARα1 and RARα2 coding exons, and that variations in RARα1/α2-PML mRNA expression likely have no clinically relevant function in APL cells.

Preliminary Results of a Consolidation Therapy Consisting Single Anthracycline Agent and Alternative All-Trans Retinoic Acid in Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4284-4284
Author(s):  
Zhang Jie ◽  
Xiaojian Meng ◽  
Zhen Cai ◽  
Xiujin Ye ◽  
He Huang
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Treatment Strategies ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Preliminary Results ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 4284 Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features that is now highly curable. However, there are complicated issues in treatment strategies for induction, consolidation and maintenance that remain to be studied. The optimal regimen and the duration of consolidation is one of the above controversies. Patients and methods: Six patients (4 males, 2 females) were enrolled in this observation with a median age of 28 years (18–36). All were diagnosed de novo APL with demonstration of the abnormal increased promyelocytes of 53–90% accompanied with detection of t(15;17) or PML/RARα rearrangements. At diagnosis, WBC counts were 0.9–4.6×109/L and platelet counts were 13–84×109/L. Induction therapy was composed of all-trans retinoic acid (ATRA) with or without anthracycline or homoharritonine. After achieving complete remission (CR) following the above regimens, consolidation therapy was given monthly consisting single anthracycline agent of idarubincin (8–10 mg/m2/d, day 1–3) or aclarubicin (8–12 mg/m2/d, day 1–7) and alternative ATRA (25 mg/m2/d, day 1–15). After 12–18 months of consolidation, patients received maintenance therapy including methotrexate (12 mg/m2/d, per week) plus 6 mercaptopurine (30 mg/m2/d, qod ×12 days) and alternative ATRA (25 mg/m2/d, day 1–15) for one year. Results and conclusions: At present, all of the six patients are in continuous CR status, four of whom ceased treatment and are undergoing regular monitoring. Preliminary results from our experience demonstrates that single anthracycline and alternative ATRA can act as a valid option with limited toxicity for APL and might be used as a consolidation strategy, particularly for low and intermediate-risk patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals New frontiers of target therapy in oncology: acute promyelocytic leukemia

2014 ◽  
Vol 31 (1) ◽  
pp. 17-28
Author(s):  
Ivan Petković ◽  
Ivica Pejčić ◽  
Svetislav Vrbić
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Target Therapy ◽  
Promyelocytic Leukemia ◽  
Hematopoietic Stem ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Optimal Drug ◽  
Risk Patients

SUMMARY By introduction of all-trans retinoic acid (ATRA) in de novo acute promyelocytic leukemia (APL) an revolution in therapy of this disease has been made. The rate of molecular complete remissions (CR) have been doubled compared to conventional chemotherapy with anthracyclines ranging from 90% to 95%. Consolidation therapy is required in order to reduce the risk of early relapse. Maintenance therapy is recommended as it further reduces the risk of relapse, especially in high-risk patients. The relapse rate in APL is relatively high, about 30% and is the most common within three years of starting the treatment. Another agent, arsenic trioxide (ATO) is the optimal drug that achieves high CR rate in relapsed, approximately 80% and hematopoietic stem cell transplantation (HSCT) may prolong the overall survival in patients with APL. ATRA and ATO have become a paradigm of targeted therapy, and APL is a paradigm of curable disease, at least in comparison to other forms of acute myeloid leukemia (AML).

Leukemic Cellular Retinoic Acid Resistance and Missense Mutations in the PML-RAR Fusion Gene After Relapse of Acute Promyelocytic Leukemia From Treatment With All-trans Retinoic Acid and Intensive Chemotherapy

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1172-1183 ◽  
Author(s):  
Wei Ding ◽  
Yun-Ping Li ◽  
Lucio M. Nobile ◽  
George Grills ◽  
Ines Carrera ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Eastern Cooperative Oncology Group ◽  
Promyelocytic Leukemia ◽  
Missense Mutations ◽  
Intensive Chemotherapy ◽  
Cellular Resistance ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract This study evaluated whether relapse of acute promyelocytic leukemia (APL) patients from clinical remissions achieved and/or maintained with all-trans retinoic acid (RA) in combination with intensive chemotherapy is associated with leukemic cellular resistance to RA and with alterations in the PML-RAR fusion gene. We studied matched pretreatment and relapse specimens from 12 patients who received variable amounts of RA, primarily in nonconcurrent combination with daunorubicin and cytarabine (DA) on Eastern Cooperative Oncology Group (ECOG) protocol E2491, and from 8 patients who received DA only on protocol E2491. Of 10 RA-treated patients evaluable for a change in APL cell sensitivity to RA-induced differentiation in vitro, 8 showed diminished sensitivity at relapse, whereas, of 6 evaluable patients treated with DA alone, only 1 had marginally reduced sensitivity. From analysis of sequences encoding the principal functional domains of the PML and RAR portions of PML-RAR, we found missense mutations in relapse specimens from 3 of 12 RA-treated patients and 0 of 8 DA-treated patients. All 3 mutations were located in the ligand binding domain (LBD) of the RAR region of PML-RAR. Relative to normal RAR1, the mutations were Leu290Val, Arg394Trp, and Met413Thr. All pretreatment analyses were normal except for a C to T base change in the 3′-untranslated (UT) region of 1 patient that was also present after relapse from DA therapy. No mutations were detected in the corresponding sequences of the normal RAR or PML (partial) alleles. Minor additional PML-RAR isoforms encoding truncated PML proteins were detected in 2 cases. We conclude that APL cellular resistance occurs with high incidence after relapse from RA + DA therapy administered in a nonconcurrent manner and that mutations in the RAR region of the PML-RAR gene are present in and likely mechanistically involved in RA resistance in a subset of these cases. © 1998 by The American Society of Hematology.

Therapy-Related Acute Promyelocytic Leukemia

2003 ◽  
Vol 21 (11) ◽  
pp. 2123-2137 ◽  
Author(s):  
M. Beaumont ◽  
M. Sanz ◽  
P.M. Carli ◽  
F. Maloisel ◽  
X. Thomas ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Acute Promyelocytic Leukemia ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Promyelocytic Leukemia ◽  
Actuarial Survival ◽  
All Trans Retinoic Acid ◽  
Primary Disorder ◽  
Primary Neoplasm ◽  
Median Interval

Purpose: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. Patients and Methods: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. Results: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin’s lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine–based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. Conclusion: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II–targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.

scholarly journals OBFC2A/RARA: a novel fusion gene in variant acute promyelocytic leukemia

Blood ◽  
2013 ◽  
Vol 121 (8) ◽  
pp. 1432-1435 ◽  
Author(s):  
Dahae Won ◽  
So Youn Shin ◽  
Chan-Jeoung Park ◽  
Seongsoo Jang ◽  
Hyun-Sook Chi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Promyelocytic Leukemia ◽  
Acid Sensitivity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Key Points

Key Points A novel fusion gene, OBFC2A/RARA, in variant acute promyelocytic leukemia. In vitro all-trans retinoic acid sensitivity.

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