8 THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 16, NO. 1, 2003
ABSTRACT
Background.High dose chemotherapy followed by autolo-
gous stem cell transplant is currently used for the treatment of
patients with advanced multiple myeloma. However, there are
no reports of the results of this treatment modality in Indian
patients.
Methods. Fifty patients with advanced multiple myeloma
underwent treatment with high dose melphalan followed by
autologous stem cell transplant (bone marrow: 7; peripheral
blood stem cells: 43). The patients’ ages ranged from 26 to 65
years (median: 52 years) and 35 were men. All patients had
receivedchemotherapyinitiallywithameanof9.4cycles(range:
1–36). Thirty patients had evidence of chemosensitive disease
at the time of transplant. The mean interval from diagnosis to
transplant was 17.5 months (range: 3–129 months) and the
mediannumberofmononuclearcellsinfusedwas4.86×10
8
per
kg (range: 2–10.48).
Results.Post-transplant, 43 of 50 patients engrafted. The
median number of days to engraftment (absolute neutrophil
count >500/cmm) was 12 (range: 9–24) and to achieve
platelet transfusion independence (>20 000/cmm) was 13
(range: 8–36). Seven patients died prior to engraftment. Grade
III–IVoralmucositiswasthemajornon-haematologicaltoxicity.
Excludingthe4patientswhohadcompleteresponsepriorto
thetransplantandcontinuedinthesamestatuspost-transplant,
31/46 patients (67%) responded; complete response was
achieved in 25 (54%) and partial response in 6 (13%). Patients
with chemosensitive disease had higher rates of complete
response; 20 of 26 patients with partial response at transplant
achievedcompleteresponsecomparedto5of20patientswith
persistent/refractory disease (p<0.01). Currently, 34 of 50
(68%) patients are alive, 17 (34%) disease-free, 6 with disease
are on salvage therapy, 11 (22%) with positive monoclonal
protein but asymptomatic are under observation. Nine (18%)
patients have died; 8 due to progressive disease and 1 of an
unrelatedcause.Themedianfollowupfortheentiregroupis26
months (range: 1–144 months). The Kaplan–Meier probability
ofoverallandprogression-freesurvivalforthewholegroupat30
months is 62%±8.11% (SE) and 42%±9.54% (SE), respec-
tively. A haemoglobin level £10 g/dl (p<0.003) affected the
High dose chemotherapy followed by autologous
haemopoietic stem cell transplant in multiple myeloma
LALIT KUMAR, G. M. K. RAJU, K. GANESSAN, S. SHAWGI, H. MENON, J. WADHWA,
A. SHARMA, RAJVEER SINGH, V. KOCHUPILLAI
survivaladversely.Chemosensitivedisease(p<0.008)attrans-
plantandcompleteresponsepost-transplant(p<0.0001)were
associatedwithsignificantlylongersurvival.
Conclusion.High dose melphalan followed by autologous
stemcelltransplantationisaneffectivetreatmentforpatientswith
advanced multiple myeloma and achievement of complete
responseisassociatedwithimprovedsurvival.
Natl Med J India 2003;16:16–21
INTRODUCTION
Multiple myeloma (MM) is a malignant disease of B cell origin
and is characterized by the presence of monoclonal plasma cells in
the bone marrow. The disease is uniformly fatal with a median
survival of 3–3.5 years.
1
Treatment with chemotherapy (melphalan
and prednisolone) has a response rate of 40%–60% with a com-
plete response (CR) in <10%.
2
Continuous infusion of vincristine
and adriamycin daily for 4 days along with dexamethasone (VAD)
or methyl prednisolone (VAMP) is associated with higher re-
sponse rates (60%–80%) and CR in 10%–20% of patients.
3,4
During the past decade, treatment with high dose chemotherapy
(HDCT) supported by autologous peripheral blood stem cell
(PBSC) transplantation has become the standard therapy for
advanced MM. This has resulted in improved response rates, and
higher overall and event-free survival compared to conventional
chemotherapy.
5–20
Though large data are available from North
America and Europe, limited data are available from developing
countries and none from India. We report our experience with 50
patients of MM treated with HDCT followed by autologous stem
cell transplantation (ASCT).
PATIENTS AND METHODS
Between April 1990 and April 2002, 50 patients (35 men) with
MM were treated with HDCT followed by ASCT; 43 of these had
ASCT between October 1995 and April 2002. The median age of
the patients was 52 years (range: 26–65 years). Table I shows the
myeloma subtypes and stage of disease in these patients. All
patients had initially received chemotherapy either with VAD
alone (n=24) or VMCP (vincristine, melphalan, cyclophospha-
mide and prednisolone) or MP (melphalan and prednisolone) or
both (n=26). The mean number of chemotherapy cycles received
was 9.4 (range: 1–36). Thirty patients (60%) had chemosensitive
disease, 20 had stable or chemoresistant or refractory disease.
Thirty-seven patients had also received radiotherapy. Sixteen
(32%) patients had renal insufficiency (serum creatinine ³2
mg/dl) at the time of diagnosis. The mean interval from diagnosis
to transplant was 17.5 months (range 3–129 months).
Transplant protocol
The initial evaluation included a detailed history, physical exami-
Institute Rotary Cancer Hospital, All India Institute of Medical Sciences,
New Delhi 110029, India
LALIT KUMAR, G. M. K. RAJU, K. GANESSAN, S. SHAWGI,
H. MENON, J. WADHWA, A. SHARMA,
V. KOCHUPILLAI Department of Medical Oncology
RAJVEER SINGH Department of Biostatistics
Correspondence to LALIT KUMAR; lalitaiims@yahoo.com
© The National Medical Journal of India 2003
Original Articles