Herbo-mineral ayurvedic treatment in a high risk acute promyelocytic leukemia patient with second relapse: 12 years follow up

Abstract

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.

Full text

Journal of Ayurveda & Integrative Medicine | July 2010 | Vol 1 | Issue 3 215
ABSTRACT
Address for correspondence:
Vaidya Balendu Prakash, Ipca Traditional Remedies Pvt. Ltd,
142 AB, Charkop Industrial Estate, Kandivli (West),
Mumbai – 400 067, India. E-mail: balenduprakash@gmail.com
Received: 02-Jun-2010
Revised: 30-Aug-2010
Accepted: 07-Sept-2010
DOI: ***
Herbo-mineral ayurvedic treatment in a high risk
acute promyelocytic leukemia patient with second
relapse: 12 years follow up
Balendu Prakash, Purvish M. Parikh1, Sanjoy K. Pal2
V C P Cancer Research Foundation (Scientic & Industrial Research Organization), Dehradun,
1AmeriCares India, Khar (West), 2IPCA Traditional Remedies Pvt Ltd., Mumbai, India
CLINICAL
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.
Key words: Ayurveda, herbo-mineral, relapse acute promyelocytic leukemia.
INTRODUCTION
Acute promyelocytic leukemia (APL) is a unique subtype
of the acute leukemias. It has distinct cytogenetics, clinical
features, and biologic characteristics. APL is caused
by arrest of leukocyte differentiation at the promyelocyte
stage. The discovery and elucidation of the molecular
pathogenesis for APL has led to the rst and only targeted
therapy for leukemia. APL is classied as AML M3 in
the French-American and British (FAB) classication
and represents approximately 5-10% of all leukemia in
adults.[1] Indian data on this malignancy are however,
limited.[2] In about 95-98% of cases, APL is associated
with the reciprocal translocation, t(15; 17)(q22; q21) and
the reciprocal fusion of the retinoic acid receptor (RAR)α
gene on chromosome 17 with the promyelocytic leukemia
(PML) gene on chromosome 15. The resulting PML-RARα
fusion gene encodes a chimeric protein that causes the
pathogenesis of APL.[1] Diagnosis of the disease is made by
examining the bone marrow. The typical phenotype of acute
promyelocytic leukemia (APL) is myeloperoxidase positive
and CD33 positive, human leukocyte antigen (HLA)-DR
negative. The disease is said to be in remission when bone
marrow study reveals no cluster or collection of blast
cells, and normal maturation of all cellular components
(i.e. erythrocytic, granulocytic, and megakaryocytic series).
There are less than 5% blast cells in the bone marrow and
none have a leukemic phenotype (e.g. Aner rods). The
persistence of dysplasia is an indicator of residual disease.
The absence of a previously detected clonal cytogenetic
abnormality (i.e. complete cytogenetic remission) conrms
the diagnosis of complete remission.
Acute myeloid leukemia (AML) is a curable disease;
the chance of cure for a specic patient depends on
a number of prognostic factors.[3] The single most
important prognostic factor in AML is cytogenetics, or
the chromosomal structure of the leukemic cell. Certain
cytogenetic abnormalities are associated with very good
CASE STUDY

216 Journal of Ayurveda & Integrative Medicine | July 2010 | Vol 1 | Issue 3
outcomes (e.g., the (15;17) translocation in APL). About
half of AML patients have normal cytogenetics; they
fall into an intermediate risk group. A number of other
cytogenetic abnormalities are known to associate with a
poor prognosis and a high risk of relapse after treatment.[4]
For patients with relapsed AML, the only proven potentially
curative therapy is a stem cell transplant, if one has not
already been performed. Patients with relapsed AML who
are not candidates for stem cell transplantion, or who
have relapsed after a stem cell transplant, may be offered
treatment in a clinical trial, as conventional treatment
options are limited.
The introduction of all-trans retinoic acid (ATRA) and,
more recently, arsenic trioxide (ATO) into the therapy of
APL has revolutionized the management and outcome of
this disease. Several treatment strategies using these agents,
usually in combination with chemotherapy, but also without
or with minimal use of cytotoxic agents, have provided
excellent therapeutic results.[5] Current state-of-the-art
treatment, which include simultaneous administration of
ATRA and anthracycline-based chemotherapy for induction
and consolidation, as well as ATRA-based maintenance, have
dramatically transformed APL into the most curable acute
leukemia in adults, with approximately 80% of long-term
survivors.[6] However, about 5%-30% of patients relapse,
mainly patients with high-risk APL.
[7] Treatment of relapsed/
advanced APL includes the use of arsenic trioxide (ATO),
gemtuzumab ozogamicin, and hematopoietic stem cell
transplantion. ATO is currently the most effective therapeutic
agent in relapsed APL. However, current therapeutic results
are still unsatisfactory in untreated patients and poorer in
those with primary refractory or relapsed disease.
Here we describe the case of a forty-seven year old patient
successfully treated with oral herbo-mineral Ayurvedic
formulations viz. Keharuba Pisti, Kamadudha Rasa, and
Navajeevan.[8] after relapsing twice with conventional
therapy. This case was part of a pilot study conducted by
the Central Council for Research in Ayurveda and Siddha
(CCRAS)[9] New Delhi in 1997. The pilot study observed
complete disease remission in 11/11 APL patients who
completed 90 days of Ayurvedic treatment.
METHODOLOGY
No direct reference to leukemia or its sub classications
has been denitely identied in the Ayurvedic literature,
though some scholars identify present day leukemia with
Raktarbuda / Raktapitta since certain symptoms of leukemia
resemble those given for these diseases. Leukemia is a
clonal, neoplastic proliferation of immature cells of the
haemopoetic system, which are classied by aberrant or
arrested differentiation. Leukemic cells rapidly accumulate
in the bone marrow cavity replacing most of normal
haemopoetic cells, resulting in signs and symptoms of
disease. The rationale for using Ayurvedic medicines
is to restore homeostasis and reverse the proliferation
of neoplastic cells in the bone marrow. Details of the
Ayurvedic medicines are given below: [Tables 1-3]:
Prakash, et al.: Ayurvedic treatment for acute pro-myelocytic leukemia
Table 1: Composition of Navajeevan*
Anupan: Water
Traditional Name English / Scientic Name Proportion
Rajat Bhasma Silver Bhasma 1 part
Jaharmohra Serpentine stone 1 part
Nirvisha Delphinium denudatum 1 part
Taruni, gulab Rosa centifolia 1 part
Chandan Santalum album 1 part
Gojihva Onosma bracteatum 1 part
Lata kasturi Hibiscus abelmoschus 1 part
* Proprietary Ayurvedic Medicine
Table 2: Composition of Kamadudha Rasa
Anupan: Mishri
Traditional Name English / Scientic Name Proportion
Mauktik Pishti Mytilus margaritiferus preparation 1 part
Pravala pisti Corallium rubrum preparation 1 part
Mukta sukti pisti Mytilus margaritiferus 1 part
Kapardika bhasma Calcinated and puried Cypraea
moneta shells
1 part
Sankha bhasma Calcinated and puried Turbinella
rapa shells
1 part
Svarna gairika Calcinated and puried Ochre 1 part
Amrta satva Tinospora cordifolia extract 1 part
Dose and administration of drug
1. Navjeevan tablet:
First three months – 250mg tablet three times daily
Next nine months – 125mg tablet three times daily
2. Kamdudha Ras (250mg) + Kehruba Pisti (125mg)
First three months – four times daily mixed with honey
Next nine months – Only Kamdudha (250 mg) three
times daily
CASE REPORT
A weak and febrile 47 years old diabetic male presented
to Tata Memorial Hospital (TMH) on 04.09.95 with
hemoglobin 5.6 gm% and total count 17,100/cu mm.
Investigation of the case at TMH conrmed diagnosis of
AML M3. His Bone Marrow Aspiration (BMA) cytology
indicated diluted cellularity; myeloid series – promyelocytes
96%; lymphocytic series and megakaryocytes were absent.
Table 3: Composition of Keharuba Pisti
Trinakanta Mani churna – 1 part
Gulab arka - Q. S. (for mardana)

Journal of Ayurveda & Integrative Medicine | July 2010 | Vol 1 | Issue 3 217
Prakash, et al.: Ayurvedic treatment for acute pro-myelocytic leukemia
Cytochemistry: a myeloperoxidase test was 100% positive.
The patient was started with ATRA for 90 days from
14.09.95, after which he developed bronchospasm, high
grade fever and odynophagia. He was treated with blood
components and antibiotics conservatively. Bone marrow
analysis carried out on 13.11.95 indicated that cellularity,
erythropoesis and myelopoesis were normal. However,
1% lymphopoesis blasts were present. His induction
chemotherapy was given from 12.01.96 to 18.01.96. Post
chemotherapy the patient had fever and vomiting; these
problems were managed conservatively. The patient then
received 3 cycles of consolidation chemotherapy with
Daunorubicin and Cytarabine combination from 12.01.96
to 14.05.96. The patient achieved clinical remission;
however, cytogenetically the disease persisted. At initial
diagnosis the patient was 100% t(15;17) positive and after
(ATRA + 4 cycle chemo) he was 50% t(15;17) positive.
For the next seven months the patient was relatively event
free. In January 97 the patient again presented to THM
for checkup. Investigations done at TMH indicated relapse
of the disease. BMA indicated cellularity – hypocellular;
erythropoesis – hyperplasia; myelopoesis – blast 2%,
abnormal promyelocytes 75%, myelocytes 10% (NEC
blast was seen), mature myelocytes 3%, band 10%. The
patient then underwent two cycles of chemotherapy
with Idarubicine and Etoposide. The first and the
second cycle were given from 18.02.97 and 18.05.97,
respectively. The patient tolerated the chemotherapy
with some side effects. For the next 6 months after
the completion of chemotherapy the patient was in
remission. The Bone marrow investigation on 12/12/97
indicated a second relapse of the disease. Blast cell 14%,
abnormal promyelocytes 85% (Faggot cells present) and
1% basophil were seen. A cytochemistry report found a
myeloperoxidase test to be 100% positive. The patient was
again advised to undergo another round of chemotherapy
with a combination of Mitoxantrone, Cytarabine and
Etoposide. However, he refused further chemotherapy
and volunteered for a pilot study conducted by the Central
Council for Research in Ayurveda and Siddha (CCRAS),[7]
and try an Ayurvedic therapy advocated by the rst author.
The patient's bone marrow slide from TMH was reviewed
at Institute of Rotary Cancer Hospital (AIIMS), New Delhi,
and he was enrolled for the study on 22.12.97.
When the Ayurvedic therapy started, the patient was very
weak, anemic, anorexic, febrile, had a lung infection and
a big rectal abscess. His hemoglobin was 7.0 gm%, total
count was 1050/cu mm, neutrophil to lymphocyte ratio was
5:95. The patient was treated conservatively with antibiotics
(oral, I.V. and local application), along with Ayurvedic
therapy. He was also given blood transfusion and human
granulocyte colony-stimulating factor to improve his WBC
count. Strict isolation was maintained, calorie rich diet
devoid of Pittavardhak aahar and salt was prescribed. After
about 15 days of alternative therapy the patient's general
condition started to improve, his lung infections subsided
and he started to maintain normal body temperature. After
1 month of therapy his differential counts started to show
a normal picture. As the patient continued with the therapy
Table 4: Details of hematological and bone marrow study of the patients
Date HB
g/dl
TLC cu/
mm
Dierential leukocyte count Plt
Cu/mm (lakhs)
ESR
mm/1 hr
Neutrophil/ Lymphocyte/Eosinophil/ Monocyte / Basophil
04.09.95 Admitted to Tata Memorial Hospital (TMH), Mumbai. APL diagnosis conrmed. Cytogenetic analysis of peripheral blood cells showed
t(15:17). Started on ATRA for 90 days. Induction and consolidation complete in TMH on 25.05.96. Complete remission of the disease
achieved.
20.05.96 6.5 8000 53/43/03/01/0 0.11
14.02.97 Relapse of the disease; Second round of chemotherapy was given which was completed in June 97; BMA after chemotherapy
indicated complete remission.
12.12.97 Bone marrow aspiration: Relapse of the disease; Blast 14% Abnormal promyelocytes 85% (Faggot cells seen), Basophil 1% .
08.01.98 6.0 59000 35/30/05/08/0/ Blast 15/ Promyelocytes 16 0.8
01.04.98 Bone marrow aspiration: No abnormal cells seen. Investigation done from Bangalore Institute of Oncology.
31.01.99 16.7 6950 49/41/08/02/0 1.3 12
19.01.00 Bone marrow biopsy and aspiration: Marrow in remission. Investigation done from Bangalore Institute of Oncology.
08.11.00 16.0 9500 64/30/04/02/0 1.8 18
14.11.00 Bone marrow aspiration: Findings are suggestive of hematological remission. Investigation done from Sir Ganga Ram Hospital, New
Delhi.
22.11.01 16.0 8400 70/24/06/0/0 1.8 10
07.11.02 15.8 8300 60/30/01/09/0 1.7 44
13.12.03 16.5 6300 59/33/07/01/0 1.58
06.11.05 14.0 6000 54/42/03/01/0 2.10 25
06.06.07 13.8 6900 65/26/04/05/0 2.05 10
13.05.09 13.3 5300 67/30/02/01/0 1.59 65
HB – hemoglobin; TLC – Total leukocyte count; Plt – Platelet count; ESR - Erythrocyte sedimentation rate.

218 Journal of Ayurveda & Integrative Medicine | July 2010 | Vol 1 | Issue 3
Prakash, et al.: Ayurvedic treatment for acute pro-myelocytic leukemia
his weakness gradually subsided. The frequency of blood
transfusion was also reduced. Before the start of Ayurvedic
therapy he had received 269 units of blood components viz.
20 units of fresh frozen plasma; 32 units of packed cells; 31
units of whole blood; 165 units of platelets concentrate and
21 units of plasma concentrate from 07.09.95 to 18.12.95.
After the start of Ayurvedic therapy the patients received
16 units of whole blood; 1 unit of packed cell and 6 units
of plasma concentrate in the rst two months of the
therapy. No further blood transfusion was required. The
Ayurvedic therapy was continued for one year and stopped.
BMA studies done after 90 days Ayurvedic treatment on
01.04.98 indicated the disease was in remission. Though
there was mild erythroid hyperplasia, granulocytic series
appeared to be normal in morphology and maturation.
No abnormal cells were seen. For the subsequent 5 years
till 2003 the patient received three months Ayurvedic
treatment every year. Subsequent, BMA performed on
19.01.2000 and 14.11.2000, respectively from Bangalore
Institute of Oncology, Bangalore and Sir Ganga Ram
Hospital, New Delhi detected no abnormality. Details of
the hematological parameters investigated during follow
up are given in Table 4. During the treatment period, and
later during follow up, the patient was constantly monitored
for liver and kidney function. The Ayurvedic treatment
did not produce any hepato or renal toxicity. In June 2002
the patient had purpuric lesions on both legs with itching
and burning sensation. His problems were managed
conservatively. At present the patient has completed 7 years
of relapse free survival after the stoppage of Ayurvedic
therapy. He is still in follow up and doing well along with
conventional management for his diabetes.
DISCUSSION
The case presented here indicates that Ayurvedic medicines
are effective in treatment of APL. The same medicines also
produced promising results in many other leukemia patients
who could not afford regular treatment.[10] Encouraging
results had been previously observed in the pilot study
conducted by CCRAS.[9]
Signicant numbers of leukemia patients in India try
various systems of complementary and alternative medicine
(CAM),[11] of which, Ayurveda is the most commonly used.
The present study indicates that the chosen Ayurvedic
medicines were effective in the treatment of APL and
did not produce any toxic side effects. As the patient did
not receive any other therapy after his second relapse, the
Ayurvedic therapy can be considered responsible for the
remission of his disease. The many APL patients who relapse
after undergoing best of conventional therapy have limited
options. An Ayurvedic approach like the one given here can
be of some help to them. However, proper clinical trials are
needed to substantiate our observations so that benecial
alternative therapies can be integrated with conventional care.
ACKNOWLEDGMENT
The support received from the Central Council for Research in
Ayurveda and Siddha, New Delhi is duly acknowledged. The
authors also like to thank Vaidya S Raghavendra Babu of Bangalore
for helping in patient management and follow up.
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Source of Support: Nil, Conict of Interest: None declared.