ArticlePDF Available

Remission in a Relapse Case of Acute Promyelocytic Leukaemia for Twenty-two years using Metal Based Ayurvedic Treatment: A Case Report

Authors:
  • VCP Cancer Research Foundation
  • Padaav Speciality Ayurvedic Treatment Center
  • Vcp cancer research center
  • VCP Cancer Research Foundation, Dehradun

Abstract

Acute Promyelocytic Leukemia (APML) is a form of blood cancer. The general symptoms of the disease include anaemia, fatigue, weakness and fever marked by thrombocytopenia, leucopenia and in some cases pancytopenia. Easy bleeding and coagulopathy associated with APML make it fatal, if not readily managed. Although new contemporary treatment options have been able to improve the prognosis in APML patients to a large extent, relapse of the disease is still noted in some cases. Also, the conventional therapies have their share of associated adverse effects and not all patients are physically and psychologically ready to bear them. Some patients, in such scenario, seek solace in alternative treatment options. In this case report, we discuss a case of APML who opted for Ayurvedic treatment in relapsed state of the disease. The patient was treated with metal based Ayurvedic formulations and achieved remission within weeks. Now the patient completes twenty-two years of disease free survival without experiencing any side effect. Chemistry, pharmacology and many other aspects related to the used Ayurvedic formulations remain unknown and need to be explored systematically.
Published by:
Director
All India Institute of Ayurveda
An Autonomous Organization under the Ministry of AYUSH, Govt. of India
Mathura Road, Gautam Puri, Sarita Vihar, New Delhi - 110076
Phone: 011-29948658
aiiaayucare@gmail.com
An Official Peer Reviewed Publication of
All India Institute of Ayurveda
New Delhi
Journal of
Ayurveda Case Reports
Journal of
Ayurveda Case Reports
Volume 2, Issue 2, April-June 2019
AyuCaRe
AyuCaRe
3
Journal of Ayurveda Case Reports Volume 2 Issue 2 April-June 2019
Journal of Ayurveda Case Reports
How to cite: Prakash B, Prakash S, Sharma S, Tiwari S.
Remission in a Relapse Case of Acute Promyelocytic
Leukaemia for Twenty-two years using Metal Based
Ayurvedic Treatment: A Case Report. J AyuCaRe
2019;2(2):3-8.
Introduction
Acute Promyelocytic Leukemia (APML), also termed
as AML-M3, is a variant of Acute Myeloid Leukemia
(AML) and accounts for 5-8% of all AMLs in adults.1 In
95-98% cases, the disease is characterised by a distinct
reciprocal translocation involving chromosome 15 and
17.2 The resulting hybrid oncoprotein known to block
the dierentiation of leukemic promyelocytes, causing
the disorder.2 APML is particularly peculiar due to its
coagulopathic nature, apart from causing leucopenia
Remission in a Relapse Case of Acute Promyelocytic Leukaemia for
Twenty-two years using Metal Based Ayurvedic Treatment: A Case Report
Balendu Prakash*, Shikha Prakash, Shakshi Sharma, Sneha Tiwari
VCPC Research Foundation, Lane C-15, Turner Road, Clement Town, Dehradun, Uarakhand
* Corresponding Author: E-mail–balenduprakash@gmail.com, Mobile: +91 9837028544
ABSTRACT
Acute Promyelocytic Leukemia (APML) is a form of blood cancer. The general
symptoms of the disease include anaemia, fatigue, weakness and fever marked by
thrombocytopenia, leucopenia and in some cases pancytopenia. Easy bleeding and
coagulopathy associated with APML make it fatal, if not readily managed. Although
new contemporary treatment options have been able to improve the prognosis in
APML patients to a large extent, relapse of the disease is still noted in some cases. Also,
the conventional therapies have their share of associated adverse eects and not all
patients are physically and psychologically ready to bear them. Some patients, in such
scenario, seek solace in alternative treatment options. In this case report, we discuss a
case of APML who opted for Ayurvedic treatment in relapsed state of the disease. The
patient was treated with metal based Ayurvedic formulations and achieved remission
within weeks. Now the patient completes twenty-two years of disease free survival
without experiencing any side eect. Chemistry, pharmacology and many other aspects
related to the used Ayurvedic formulations remain unknown and need to be explored
systematically.
Key words
Ayurveda,
Leucopenia,
Leukemia,
Thrombocytopenia
and pancytopenia can be fatal if not diagnosed and
managed timely.3 Investigations done to diagnose
APML include complete blood count and bone marrow
aspiration. Immunophenotyping and cytogenetic tests
may also be carried to decipher the exact type and
course of the disease.
APML is most common in adults in their midlife and
has rare incidences in adults more than 60 years of
age.4 Although APML has overall incidences as low as
0.1/100,000 the disease was considered the most fatal
form of leukaemia with severe bleeding tendency.5 But
with the advent of all-trans retinoic acid (ATRA) and,
more recently, arsenic trioxide (ATO) with or without
chemotherapy in the treatment of APML; the disease
has now evolved as one of the most curable forms of
4 Journal of Ayurveda Case Reports Volume 2 Issue 2 April-June 2019
Prakash B, et al.: Ayurvedic Management or Acute Promyelocytic Leukaemia
leukaemia with 90% remission rates and more than
80% disease free survival rate at six years especially
among low risk groups.6-7 A study carried for a ten years
median period, shows ten year disease free survival
in 77% cases.8 In spite of the improving survival rates,
10-15% relapse rates of APML are still reported.9 The
relapse cases are again treated using ATRA, ATO or a
combination of these with or without chemotherapy,
and stem cell transplantation, whenever possible.7
However, despite yielding promising results, these
therapies pose certain side eects ranging from
severe hematologic toxicity to hyperleukocytosis and
even occurrence of secondary myeloid neoplasms
in few cases.10 Dierentiation syndrome is the most
common and potentially life threatening treatment
related complication associated with these therapies.
Its symptoms include dyspnea, unexplained fever,
hypotension, kidney damage, weight gain and peripheral
edema. Prolongation in QT interval of the cardiac cycle
is another common side eect of ATO therapy.10 Hence,
patients still remain unsatised with the treatment
possibilities for APML and look for alternative treatment
options.
Data on duration of disease free survival in post relapse
cases of APML is limited with the longest known follow
up of twelve years in a case of post second relapse of
the disease treated using herbo–mineral Ayurvedic
formulations.11 Here, a case that opted for Ayurvedic
treatment in a relapsed state of APML under an
Ayurvedic physician in North India has been presented.
Case report
The 33 years old male from New Delhi presented to Tata
Memorial Hospital, Mumbai in April 1994 (Reference
No. BH6477) with fever and abnormal blood prole.
Investigations revealed features of Acute Promyelocytic
Leukemia (ICD 10 code: C92.4) with 96% promyelocytes.
He was treated with oral ATRA for 90 days. He achieved
complete remission after rst three weeks of treatment.
Subsequently, he received four cycles of chemotherapy
between July to November 1994. Bone marrow study
done in January 1995 showed complete remission but
20% metaphases showed presence of t(15;17). Meanwhile,
the patient also developed diabetes mellitus. The disease
relapsed in June 1995 when in follow up investigations,
his Bone Marrow Aspirate (BMA) showed 14% blasts and
50% promyelocytes (Ref No. 208695006; Lab No. E-1492,
Tata Memorial Hospital, Mumbai dated 19-06-1995). The
patient was explained for poor prognosis and advised
to undergo further chemotherapy. Patient and his close
family denied pursuing modern medicines and, instead,
opted for Ayurvedic treatment.
Treatment protocol
The patient presented to the Ayurvedic clinic with
high fever. He had pancytopenia, lymphocytosis, and
Plasmodium vivax infection. Ayurvedic treatment was
started on 14th September 1995 and malarial infection
was managed conservatively. He was advised to take
nearly 2000 calorie diet daily, comprising of a balance
of carbohydrates, proteins and dairy, divided into three
meals and three snacks with eight hours of sleep at night.
The patient was kept in strict isolation with complete
psychological and physical rest. He was restricted from
taking tea, coee, packaged foods and drinks, reheated
food, rened our, onion, garlic and tomatoes. He was
prescribed oral Ayurvedic formulations; Navajeevan11-12
(250 mg three times a day) with water, Kamadudha rasa
powder11,13 (250 mg thrice a day) orally, 21 Tulsi patra
(thrice a day) and Pancharatni arka (50 ml four times a
day), for the initial one month. Later, the medicines and
doses were adjusted periodically as per the clinical signs
and symptoms. Arka (~distillate) of Chandana (Santalum
album Linn.), Gojihva (Onosma bracteatum Wall.) and
Gulab (Rosa centifolia Linn.) (50 ml twice a day) was
prescribed. (Table 1) Pancharatni arka was made up of
200 gm each of Ajmoda (Trachyspermum ammi Linn.),
Khoob kalan [Sysimbrium ocinalis (L) Scop.], Pia papda
[Fumaria indica (Hausskn.)], fresh Guduchi [Tinospora
cordifolia (Willd.) Miers], Katumba jad or Gumma jad
(Leucas cephalotes spreng.) processed in 16 litres of water.
The treatment was carried for 340 days.
Outcome
Marked improvement was noted in the patient after
starting Ayurvedic treatment. Fever subsided within
fteen days of treatment. 35% promyelocytes that were
seen in the blood smear started reducing gradually. The
results of complete blood count (CBC) done on 28th October
5
Journal of Ayurveda Case Reports Volume 2 Issue 2 April-June 2019
Prakash B, et al.: Ayurvedic Management or Acute Promyelocytic Leukaemia
Table 1: Details of Ayurvedic formulations prescribed and periodic changes in prescription
Day of treatment Prescription
Day 0 1. Navajeevan (250 mg) tablet thrice a day with water
2. Kamdudha rasa (250 mg) powder thrice a day
3. Tulsi patra 21 leaves thrice a day
4. Pancharatni arka 50 ml four times a day
Day 30 1. Navajeevan (125 mg) tablet thrice a day with water
2. Kamdudha rasa (250 mg) powder thrice a day
3. Pancharatni arka 50 ml four times a day
Day 105 1. Navajeevan (125 mg) tablet twice a day with water
2. Kamdudha rasa (250 mg) powder thrice a day
3. Arka of Chandan + Gojihva + Gulab 50 ml twice a day
Day 150 1. Navajeevan (125 mg) tablet twice a day with water
2. Kamdudha rasa (250 mg) powder thrice a day
3. Prak 2011 500 mg capsule thrice a day with water
4. Arka of chandan + Gojihva + Gulab 50 ml twice a day
Day 270 1. Navajeevan (125 mg) tablet twice a day with water
Day 300 1. Navajeevan (125 mg) tablet twice a day with water
2. Arka of chandan + Gojihva + Gulab 50 ml twice a day
1995 depicted no abnormal cells. Bone marrow aspiration
done after fteen months of starting of Ayurvedic
treatment indicated less than 5% promyelocyte and blast
cells, indicating complete remission of the disease (BMA
done at dated 31/01/1997). The treatment was given
for a period of 340 days, following which he had been
under continuous monitoring. No grade II toxicity of
the treatment was reported in the patient. Subsequent
BMAs showed complete remission of the disease.
He was advised to get blood tests done periodically.
(Graph 1-3) The results of these studies indicate
sustainable improvement in the patient and the patient
is leading a normal life now.
Discussion
Ayurvedic texts have no direct reference of leukaemia.
However, its symptoms have been at times linked to
those of Rakta pia.14 Dhatuvigyana (~science of metals),
under Rasa shastra, emphasises upon the importance of
equilibrium of the seven Dhatus including Gold, Silver,
Copper, Iron, Tin, Lead and Zinc, within the body for
healthy metabolism. The body is made up of seven
Dhatus (
~
tissues). Any imbalance between these Dhatus
leads to initiation of disease process within the body.1
5
Navajeevan is a proprietary formulation based on the
principles of Rasa shastra.16 It is prepared using equal
parts of Rajata bhasma (~calcined silver), Jawahar mohra
(~serpentine stone) pishti and Nirvishi (Delphinium
denudatum Wall.) roots with distillate of Gulab (Rosa
centifolia Linn.), Chandana (Santalum album Linn.),
Gojihva (Onosma bracteatum Wall.) and Lata kasturi
(Hibiscus abelmoschus Linn.). Rajata (~silver) is present
in Majja (~bone marrow) and its imbalance might
disturb the production of many blood components.15
Nirvishi has been described in Ayurvedic texts to have
blood purifying properties. It is used to eliminate eect
of Dushi visha and is also Tridosha shamaka.17 Jawahar
mohra is also used in Pia related disorders and has the
property to eliminate Dushi visha. Kamadudha rasa is a
6 Journal of Ayurveda Case Reports Volume 2 Issue 2 April-June 2019
Prakash B, et al.: Ayurvedic Management or Acute Promyelocytic Leukaemia
Graph 1: Eect of Ayurvedic treatment on total leucocyte count as depicted in periodical blood tests.
Graph 3: Eect of Ayurvedic treatment on total lymphocyte count as observed in periodical blood
count repots.
Graph 2: Eect of Ayurvedic treatment on platelet count.
TLC (/mm3)
Normal range
16000
14000
12000
10000
8000
6000
4000
2000
0
06-09-1995
20-09-1995
26-09-1995
30-09-1995
09-10-1995
11-11-1995
08-12-1995
08-01-1996
14-02-1996
12-03-1996
07-05-1996
14-06-1996
01-07-1996
14-08-1996
11-09-1996
10-10-1996
02-11-1996
28-01-1997
14-02-1997
14-04-1997
07-06-1997
06-09-1997
17-10-1997
29-08-1998
30-01-1999
16-09-1999
24-01-2000
06-04-2000
07-02-2001
12-03-2002
11-12-2008
23-01-2010
07-10-2011
30-07-2012
02-05-2013
28-09-2017
06-09-1995
20-09-1995
26-09-1995
30-09-1995
09-10-1995
11-11-1995
08-12-1995
08-01-1996
14-02-1996
12-03-1996
07-05-1996
14-06-1996
01-07-1996
14-08-1996
11-09-1996
10-10-1996
02-11-1996
28-01-1997
14-02-1997
14-04-1997
07-06-1997
06-09-1997
17-10-1997
29-08-1998
30-01-1999
16-09-1999
24-01-2000
06-04-2000
07-02-2001
12-03-2002
11-12-2008
23-01-2010
07-10-2011
30-07-2012
28-09-2017
80
70
60
50
40
30
20
10
0
Lymphocytes (%)
Normal range
Platelet count (thou/mm3)
06-09-1995
20-09-1995
26-09-1995
30-09-1995
09-10-1995
11-11-1995
08-12-1995
08-01-1996
14-02-1996
12-03-1996
07-05-1996
14-06-1996
01-07-1996
14-08-1996
11-09-1996
10-10-1996
02-11-1996
28-01-1997
14-02-1997
14-04-1997
07-06-1997
06-09-1997
17-10-1997
29-08-1998
30-01-1999
16-09-1999
24-01-2000
06-04-2000
07-02-2001
12-03-2002
11-12-2008
23-01-2010
07-10-2011
30-07-2012
02-05-2013
28-09-2017
400
350
300
250
200
150
100
50
0
Normal range
7
Journal of Ayurveda Case Reports Volume 2 Issue 2 April-June 2019
Prakash B, et al.: Ayurvedic Management or Acute Promyelocytic Leukaemia
classical Ayurvedic formulation that is known to restore
the balance of Pia in the body.
The aforesaid formulations with a diet rich in dairy,
seasonal cereals, pulses, fruits and vegetables, low salt
intake and devoid of tea, coee, aerated drinks, reheated
and packed food, was probably able to alter the natural
history of the disease and bring twenty-two years long
ongoing disease free survival without causing any
grade II toxicity. The eect observed in the case study
can be explained hypothetically at this point as intrigue
chemistry of Ayurvedic formulations. However, the
periodical bone marrow examinations, blood prole and
clinical condition of the patient continue to depict long
term therapeutic eect of Ayurvedic formulations in
the successful and sustainable management of relapsed
state of APML.
Rasa shastra that deals with prevention and treatment
of many diseases also deals with Mercury and specied
substances of mineral, plant and animal origin. Most
of these ingredients are moderate to severely toxic
in raw forms. However, tedious methodology not
only eliminates their toxic eect but also converts a
combination of these into a life saviour compound.
This particular branch of Ayurveda has not been much
explored for its therapeutic properties. However,
such anecdotal cases do suggest that it needs to be
investigated thoroughly and larger studies should be
carried to establish the role of the stated formulations
in the management of APML or related disorders. The
medicines stated have also earlier shown encouraging
results in a pilot study conducted under the aegis of
Central Council of Research in Ayurvedic Sciences.18
Conclusion
This case report is a proof of the therapeutic ecacy of
the stated Ayurvedic formulations in the treatment of
APML and needs further merit.
Source of support
None.
Conict of Interest
Both the formulations used in this case are being
prescribed by the corresponding author in his clinical
practice since years. There is no other conict of
interest.
Acknowledgements
We duly acknowledge Late Vaidya Chandra Prakash for
evolving this formula and the patient with his family for
sharing the medical details.
References
1. Adams J, Nassiri M. Acute promyelocytic
leukemia. Arch Pathol Lab Med. 2015;139:1308-13.
2. Kotiah SD, Besa EC. Acute promyelocytic
leukemia clinical presentation. Medscape drugs
& diseases. 2015. hp://emedicine.medscape.com/
article/1495306-clinical.
3. Akhtar K, Ahmad S, Sherwani RK. Acute
promyelocytic leukemia, hypogranular variant:
a rare presentation. Clinics and Practice
2011;1(1):e11.
4. Shah MA, Gupta A, Kaur S. A retrospective study
of acute promyelocytic leukemia. IOSR Journal of
Pharmacy 2012;2(6):52-9.
5. Sant M, Allemani C, Tereanu C, De Angelis
R, Capocaccia R, Visser O, et al. Incidence
of hematologic malignancies in Europe by
morphologic subtype: results of the HAEMACARE
project. Blood 2010;116(19):3724-34.
6. Coombs CC, Tavakkoli M, Tallman MS. Acute
promyelocytic leukemia: where did we start,
where are we now, and the future. Blood Cancer J.
2015;17(5):e304.
7. Azevedo IF, Magalhaes MG, Souto FR, Neves
WB, Melo FC, Rego EM, et al. Molecular and
hematologic relapses in adult patients with
acute promyelocytic leukemia: a cohort study.
Revista Brasileira de Hematologia e Hemoterapia
2017;39(1):46-51.
8. Ades L1, Guerci A, Raoux E, Sanz M, Chevallier
P, Lapusan S, et al. Very long-term outcome of
acute promyelocytic leukemia after treatment
with all-trans retinoic acid and chemotherapy:
the European APL Group experience. Blood
2010;115(9):1690-6.
9. Hessenauer M, Farhadfar N, Gangat N. Incidence
8 Journal of Ayurveda Case Reports Volume 2 Issue 2 April-June 2019
Prakash B, et al.: Ayurvedic Management or Acute Promyelocytic Leukaemia
and management of relapsed acute promyelocytic
leukemia. Blood 2016;128(22):5179.
10. Cicconi L, Lo-Coco F. Current management of
newly diagnosed acute promyelocytic leukemia.
Annal of oncology 2016;27:1474-81.
11. Prakash B, Parikh P, Pal SK. Herbo-mineral
Ayurvedic treatment in a high risk acute
promyelocytic leukemia patient with second
relapse: 12 years follow up. J Ayurveda Integr
Med. 2010;1(3):215-8.
12. Prakash B. Indigenous approach to combat cancer.
Health Administrator 2005;17:169-71.
13. Anonymous. Rasatantrasara va Siddhaprayoga
Sangraha. Part:1, Kharaliya rasayana no. 80. Ajmer:
Krishna Gopal Ayurveda Bhavan; 1980. p. 444-5.
14. Upadhyaya Y, editor. Madhava nidana of
Madhava, Part 1. 13th ed. Varanasi: Chaukhambha
Sanskrit Sansthan; 1981. p. 236.
15. Pal SK. A review on an Ayurvedic approach for
cancer treatment developed by Vaidya Balendu
Prakash. Int Jour of Interdisc and Multidisc Studies
2014, Vol 1, No. 6, 1-11.
16. Savrikar SS, Ravishankar B. Introduction to
Rasa shastra the Iatrochemistry of Ayurveda.
Afr J Tradit Complement Altern Med.
2011;8(5Suppl):66-82.
17. Nizami Q, Jafri MA. Unani drug Jadwar
(Delphinum denudatum wall) - A review. Indian
Journal of Traditional Knowledge. 2006;5(4):463-7.
18. Prakash VB. Eect of metal based Ayurvedic
formulations in the patients of acute
promyelocytic leukemia a pilot study.
Monograph submied to Central Council
for Research in Ayurveda & Siddha, New
Delhi. 2003. Available at: hps://ayurinfo.
files.wordpress.com/2013/07/metal-based-
ayurvedic-formulations-in-acute-apml.pdf./ last
accessed on 03/08/2019 at 16:08.
All India Institute of Ayurveda (AIIA), conceived as an apex Ayurveda institute
under Ministry of AYUSH with a vision to be an outstanding center of excellence
for Ayurveda Education, Research and Healthcare. It is a perfect blend of Ancient
wisdom and Modern technology, aracting global aention and expected to boost
medical tourism in India showcasing strengths of Ayurveda.
Published by:
Director
All India Institute of Ayurveda
An Autonomous Organization under the Ministry of AYUSH, Govt. of India
Mathura Road, Gautam Puri, Sarita Vihar, New Delhi - 110076
Phone: 011-29948658
aiiaayucare@gmail.com
An Official Peer Reviewed Publication of
All India Institute of Ayurveda
New Delhi
Journal of
Ayurveda Case Reports
Journal of
Ayurveda Case Reports
Volume 2, Issue 2, April-June 2019
AyuCaRe
AyuCaRe
Article
Full-text available
Acute myeloid leukemia (AML) is malignancy of the stem cell precursors of the myeloid lineage, occurs due to variations in genetics. In Ayurveda AML, can be considered into Raktapitta (~bleeding disorder) disease. Hemidesmus indicus (L.) R.Br. (~H. indicus) is described for treatment of Raktapitta. This study establish link for therapeutic activity of H. indicus in AML using Network pharmacology and molecular docking study. Active compound from root of H. indicus was retrieved from phytochemical based IMPPAT database. ADME (absorption, distribution, metabolism and excretion) done with SwissADME database, and target of active compound were obtained with SwissTargetPrediction database. Target of AML retrieved from GeneCard database. Cytoscape3.9.1 software was used to construct the "drug-active components-target" network diagram from common targets. The PPI (protein-protein interaction) network between proteins was constructed by STRING and result exported to Cytoscape3.9.1 for network analysis to get subnetwork with key target of subnetwork and core targets of overall PPI. GO and KEGG pathway analysis of key target from subnetwork done with g-profiler database. Core targets were docked with their corresponding active compound to get docking score. All core targets identified through network analysis of PPI network were linked to common active compound quercetin, and on molecular docking study all core targets showed good docking score to quercetin. Hence, based on this study conclusion can be drawn that the activity of H. indicus is AML might be due to presence of quercetin active compound in it. This study generated link for usefulness of H. indicus is AML.
Article
Full-text available
Acute 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.
Article
Full-text available
Objective To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy. Methods The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction. Results Eighty-nine patients were diagnosed with acute promyelocytic leukemia over a seven-year period and of these 65 were eligible for treatment with the protocol. Among the 45 patients who received consolidation and maintenance treatment, six (13%) relapsed, three of whom presented hematologic and three presented molecular relapse. The first relapses occurred at a median of 39 months. Relapsed patients were from all risk groups (low, intermediate and high) and both morphological types (M3 and M3variant) were found. Three of these patients are alive and in molecular remission after salvage treatment. There were no statistically significant differences regarding gender, age, risk group, morphology, promyelocytic leukemia breakpoint cluster region, use of all-trans retinoic acid, development of differentiation syndrome and number of days to complete remission between the patients who relapsed and those who did not. Conclusion Our results reinforce the importance of prolonged monitoring of acute promyelocytic leukemia patients using molecular methods to detect relapse early.
Article
Full-text available
The majority of patients with acute promyelocytic leukemia (APL) manifest the t(15;17)(q24.1;q21.2) translocation; however, a minor but significant proportion of patients with APL harbor complex, cryptic, or variant translocations, which typically involve RARA. With the exception of ZBTB16/RARA, these variants have similar morphologic and immunophenotypic features as classic APL. Study of the variant forms of APL not only gives insight into the pathogenesis of APL but also allows us to understand the mechanism of retinoid therapy. It is important to identify these cryptic and variant translocations because certain variants, including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans retinoic acid, arsenic trioxide, and anthracyclines.
Article
Full-text available
Historically, acute promyelocytic leukemia (APL) was considered to be one of the most fatal forms of acute leukemia with poor outcomes before the introduction of the vitamin A derivative all-trans retinoic acid (ATRA). With considerable advances in therapy, including the introduction of ATRA initially as a single agent and then in combination with anthracyclines, and more recently by development of arsenic trioxide (ATO)-containing regimens, APL is now characterized by complete remission rates of 90% and cure rates of ~80%, even higher among low-risk patients. Furthermore, with ATRA-ATO combinations, chemotherapy may safely be omitted in low-risk patients. The disease is now considered to be the most curable subtype of acute myeloid leukemia (AML) in adults. Nevertheless, APL remains associated with a significant incidence of early death related to the characteristic bleeding diathesis. Early death, rather than resistant disease so common in all other subtypes of AML, has emerged as the major cause of treatment failure.
Article
Full-text available
Early diagnosis of acute promyelocytic leukemia (APL) is essential because of its associated life threatening coagulopathy and unique response to all trans-retinoic acid (ATRA) therapy. The characteristic cell morphology supplemented by cytochemistry offers the most rapid means for diagnosis. Here we describe a rare case of acute promyelocytic leukemia-hypogranular variant that poses particular diagnostic challenge.
Article
Full-text available
The word Rasashaastra literally means the "Science of Mercury". It is a specialized branch of Ayurveda dealing mainly with materials which are known as 'Rasa dravyaas'. The products dealt under this discipline are an important component of Ayurvedic therapeutics. Considering the importance of this discipline in Ayurvedic therapeutics and the fact that there is dearth of comprehensive review on the subject an attempt has been made in this review to provide a brief but all encompassing coverage of different aspects related to it. The subjects covered in the review are: historical background of the evolvement of Rasashaastra as a specialized branch during different time periods; different aspects of classification 'Rasa dravyaas'; processing of metal and mineral products with a note on the methods used during different time periods; information about methods of pre and post preparation procedures for different kinds of 'Rasa dravyaas'; importance of mercury in Ayurveda, its processing methods and different preparations along with therapeutic indications. In addition attempt has been made to provide basic information on the metal and mineral based preparations mentioned in Ayurvedic Formulary of India; recent development in the field of Rasashaastra and future requirements for the proper development of the discipline. The main focus is to familiarize the readers, from non-ayurvedic background, on different aspects of this specialized discipline.
Article
Full-text available
A 47 year old diabetic male patient was diagnosed and treated for high risk AML-M3 at Tata Memorial Hospital (BJ 17572), Mumbai in September 1995. His bone marrow aspiration cytology indicated 96% promyelocytes with abnormal forms, absence of lymphocytic series and myeloperoxide test 100% positive. Initially treated with ATRA, he achieved hematological remission on day 60, but cytogenetically the disease persisted. The patient received induction and consolidated chemotherapy with Daunorubicin and Cytarabine combination from 12.01.96 to 14.05.96, following which he achieved remission. However, his disease relapsed in February 97. The patient was given two cycles of chemotherapy with Idarubicine and Etoposide, after which he achieved remission. His disease again relapsed in December 97. The patient then refused more chemotherapy and volunteered for a pilot Ayurvedic study conducted by the Central Council for Research in Ayurveda and Siddha, New Delhi. The patient was treated with a proprietary Ayurvedic medicine Navajeevan, Kamadudha Rasa and Keharuba Pisti for one year. For the subsequent 5 years the patient received three months of intermittent Ayurvedic treatment every year. The patient achieved complete disease remission with the alternative treatment without any adverse side effects. The patient has so far completed 13 years of survival after the start of Ayurvedic therapy.
Article
Full-text available
Changing definitions and classifications of hematologic malignancies (HMs) complicate incidence comparisons. HAEMACARE classified HMs into groupings consistent with the latest World Health Organization classification and useful for epidemiologic and public health purposes. We present crude, age-specific and age-standardized incidence rates for European HMs according to these groupings, estimated from 66,371 lymphoid malignancies (LMs) and 21,796 myeloid malignancies (MMs) registered in 2000-2002 by 44 European cancer registries, grouped into 5 regions. Age-standardized incidence rates were 24.5 (per 100,000) for LMs and 7.55 for MMs. The commonest LMs were plasma cell neoplasms (4.62), small B-cell lymphocytic lymphoma/chronic lymphatic leukemia (3.79), diffuse B-cell lymphoma (3.13), and Hodgkin lymphoma (2.41). The commonest MMs were acute myeloid leukemia (2.96), other myeloproliferative neoplasms (1.76), and myelodysplastic syndrome (1.24). Unknown morphology LMs were commonest in Northern Europe (7.53); unknown morphology MMs were commonest in Southern Europe (0.73). Overall incidence was lowest in Eastern Europe and lower in women than in men. For most LMs, incidence was highest in Southern Europe; for MMs incidence was highest in the United Kingdom and Ireland. Differences in diagnostic and registration criteria are an important cause of incidence variation; however, different distribution of HM risk factors also contributes. The quality of population-based HM data needs further improvement.
Article
2088 Poster Board II-65 Background APL is highly curable with the combination of ATRA and anthracycline based chemotherapy (CT), but very long term results of this treatment remain unpublished. We present here the very long term results of APL93, that included newly diagnosed patients ( pts) between 1993 and 1998, with a 10 year median follow-up, particularly focusing on late events. Methods For induction treatment. Pts aged ≤65 years with WBC < 5,000/μL were randomized between ATRA 45 mg/m2/d followed by CT (DNR 60 mg/m2/d × 3 d + AraC 200 mg/m2/d for 7 d :ATRA→CT group) or ATRA plus CT (ATRA+CT), where the same CT was started on day 3 of ATRA treatment. After CR achievement, they received 2 consolidation courses of DNR and AraC (the first identical to the induction course, the second with DNR 45 mg/m2/d for 3 days and 1g/m2/12h AraC for 4 days). Pts with baseline WBC> 5,000/μL (irrespective of their age) and pts aged 66-75 years with WBC count ≤ 5,000/μL were not randomized but received ATRA with addition of CT on day 1 of ATRA treatment (high WBC group) and the same schedule as in the ATRA→CT group (elderly group), respectively. The elderly group received only the first consolidation course. For maintenance, pts were randomized to receive or not (2×2 analysis) intermittent ATRA (45 mg/m2 /d, 15 days every 3 months) and to receive or not continuous CT with 6MP (90 mg/m 2 /d, orally) and MTX (15 mg/m 2 /wk, orally) scheduled for 2 years. Interim results of this trial have been published (Blood 1999, vol 94, 1192-200). Results In the 576 APL included, the CR rate was 87.3% and 90.7% in the elderly and the high WBC groups, respectively (resp), and ,in randomized pts, was 92.6% and 96.2% in the ATRA→CT and ATRA+CT groups , resp(p= 0.19). With a median follow-up of 121 months, 142 (26.6%) pts had relapsed, 59 (11%) had died in CR and 329 (61.7%) remained in first CR. 18 (12.7% of the relapses, 3.3% of the patients in CR), 9 and 3 relapses occurred after 4, 6 and 8 years, resp. Based on initial stratification, the 10-year cumulative incidence of relapse (CIR) was 16.5% in pts <65 years with WBC<5,000/μl, 37.9% in the high WBC group and 9.3% in the elderly group (p<0.0001). 10-year OS was 77% in the whole population, and 78.6%, 63.1% and 58.1% in randomized, high WBC and elderly groups, resp (p<0.0001). In pts <65 years with WBC<5,000/μl ( ie randomized at diagnosis), , 10-year EFS (primary end point of the 1stRandomization) was 64.4% in the ATRA→CT group and 76.3% in the ATRA+CT group (p=0.019), 10-year CIR was 21.6% in the ATRA→CT group and 13.2% in the ATRA+CT group (p=0.087); and 10-year OS was 81.8% vs. 85.0% in the ATRA→CT and ATRA+CT groups, respectively (p=0.23). Regarding maintenance, 10-year CIR (Primary endpoint of the 2ndrandomization) was 43.2%, 33%, 23.4% and 13.4%, after no maintenance, maintenance with ATRA alone, CT alone and both, resp (p<0.0001). In pts with WBC >5,000/μl, the 10-year CIR was 68.4%, 53.1%, 32.8% and 20.6% with no maintenance, ATRA alone, CT alone and both, resp (p < 0.0001). In pts with WBC < 5000/μL, the 10-year CIR was 29.2%, 22.9%, 21.0% and 11.5% with no maintenance, ATRA alone, CT alone and both, respectively (p =0.069). 41/322 pts received maintenance <1 yr due to side effects or to patient or physician's decision. Hazard of relapse was significantly increased in pts who received maintenance <1 yr vs > 1 yr (HR= 0.16 p< 0.0001). 59 patients (11%) died in first CR ( 10-year cum incidence (CI) of 5.7%, 15.4% and 21.7% in patients aged < 55, 55-65 , > 65 y, resp). Sepsis secondary to neutropenia (occurring during consolidation but also in 6 cases, during maintenance) and solid tumors accounted for 39% and 15% of death in CR, respectively. CI of secondary tumors and MDS was 1.4% and 0.2% at 5 years, 2.7% and 1.1% at 10 years. Conclusion Our results with a median follow-up of 10 years, confirm that the combination of ATRA and chemotherapy can cure > 75% of APL and show the long term usefulness of sufficiently prolonged maintenance treatment, particularly in pts with initial WBC counts >5000/μl and, in pts with WBC counts <5000/ul, the probable benefit of early addition of CT to ATRA. Very few long-term complications were seen. However, reduction of the incidence of deaths in CR in this highly curative disease is mandatory and requires reduction in the use of myelosuppressive drugs. Disclosures No relevant conflicts of interest to declare.
Article
The management of Acute Promyelocytic Leukemia (APL) has considerably evolved during the past two decades. The advent of All-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA-chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleucocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APremains a challenging condition which needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated to modern treatment of the disease.