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Autologous Bone Marrow TransplantationThe Autologous Bone Marrow Transplant Registry (ABMTR) estimates that 30 000autologous bone marrow transplants were performed in 1997 by the 250 centres thatreported their data to the ABMTR.I This is almost twice the number of allogeneictransplants performed and reported for the same year. The source of stem cells usedto be the bone marrow but recently most centres have been using stem cells collectedfrom the peripheral blood; these are called peripheral blood stem cell or progenitorcell transplants (PBSCTIPBPCT). The use of mobilized peripheral blood progenitorcells (PBPC) has resulted in more rapid engraftment, shorter hospital stay anddecreased medical costs than using non-mobilized bone marrow.' Some workers usethe term autologous haematopoietic cell transplants (AHCT) to encompass all theseforms of transplants.

Stem cells are mobilized into the peripheral blood either by chemotherapy or bythe administration of growth factors. Autologous transplants are performed for thosediseases where effective chemotherapy is available but the main dose-limiting toxi-city is myelosuppression. It makes sense to collect the marrow or stem cells, cryo-preserve them, administer the drug combination and then restore haematopoiesis byre-infusing the stored stem cells. A prerequisite for the success of this treatmentapproach would be that the stem cells should not be contaminated with tumour cellsor, if present, they should be in such small numbers that the host can eliminate thesecells. Alternatively, the collected stem cells should be purged of contaminatingtumour cells by some means. Cryopreservation is believed to confer a selectivesurvi val advantage to stem cells, thereby reducing the number of tumour cells in thetransplanted product after thawing.' Purging with chemotherapeutic agents such ashydroperoxycyclophosphamide which are not toxic to stem cells or using tumour-specific monoclonal antibodies is another way of decreasing tumour contaminationin the stem cells to be transplanted." Concentration of CD34-positive stem cells usingmonoclonal antibodies to CD34 tagged with iron particles and positive selection bymagnetic fields is also a means of achieving a 2 log reduction of contaminatingtumour cells.' Some trials have shown a significant reduction in relapse rates whenpurging techniques have been employed, but engraftment is delayed with increasedmorbidity."

Advances in stem cell collection, cryopreservation and management of the patientwith blood component support and prevention and treatment of infection has madePBSCT safe, with most good centres reporting a procedure-related mortality of lessthan 10%.7 In fact, some centres now perform PBSCT as an outpatient procedure andalso treat older patients." Compared to allogeneic stem cell transplants, AHCT doesnot have the problems of graft-versus-host disease but there is also no graft-versus-tumour effect, which is one of the main ways a transplant is effective in eradicatingmalignant cells in conditions such as chronic myeloid leukaemia.

Autologous stem cell transplants are performed for the following haematologicalmalignancies: acute leukaemia, lymphoma and multiple myeloma. In the primarytreatment of acute myeloid leukaemia, two randomized trials9,IO showed no differencebetween intensive chemotherapy, ABMT and allogeneic BMT while Zittoun et al,"report leukaemia-free survival (LFS) at 4 years of 48% for ABMTv. 30% for intensivechemotherapy. 12The role of ABMT in the primary treatment of acute lymphoblasticleukaemia is less certain with only a few studies showing benefit." In patients withrelapsed and refractory intermediate grade non-Hodgkin's lymphoma, conventionalsalvage chemotherapy may rescue 10% of patients while AHCT can achieve adisease-free survival (DFS) of 36% in chemo-sensitive patients and 14% in patientswith chemo-resistant disease.":" For patients with relapsed Hodgkin's lymphoma,AHCT offers a 50% probability of progression-free survival at 5 years, which is betterthan the best salvage chemotherapy .16In multiple myeloma, the addition of an auto-transplant to the chemotherapeutic regimen increases the complete remission rate andDFS but it is doubtful whether the overall survival is increased, 17,18Barlogie et al. intheir total therapy programme consisting of cyclical intensive chemotherapy fol-

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lowed by tandem transplants were able to obtain a complete remission (CR) in 41%of patients who could receive the second transplant." This approach is likely toimprove the overall survival, since 20% of patients achieving CR have not relapsedat 10 years after a single total body irradiation-based autotransplant."

Autotransplants are also performed for solid tumours, mainly breast, ovary, smallcell carcinoma of the lung and germ cell tumours. One-third of all the transplantsperformed in the USA are for breast cancer. ABMT is used in patients with solidtumours either in metastatic or recurrent disease or as an adjuvant to surgery and/orstandard chemotherapy in patients with a known high risk of recurrence. Proponentsof AHCT in breast cancer feel that a DFS of 10%-20% can be achieved in patientswith metastatic breast cancer compared to 1.3% with conventional chemotherapy."However, there are few randomized trials comparing standard approaches withautotransplants in a uniform group of patients with solid tumours." In fact, someinvestigators consider the use of ABMT in invasive breast cancer as experimentalwith little evidence to support benefit and a low cost utility (US$ 100 000 for everyadditional quality year gained)." AHCT is currently being investigated in themanagement of refractory autoimmune diseases with some striking results."

In this issue of the Journal, Guptaet at. 25 report on their experience with AHCT atthe All India Institute of Medical Sciences, New Delhi. Their patient group is tooheterogeneous and the numbers too small to draw any conclusions on the survivaladvantage of the intervention. The failure to achieve engraftment in 19% of thepatients is of concern but with experience this incidence would certainly decrease.

Autologous stem cell transplants should be available in tertiary referral institutionsin India. These centres should do a sufficient number of procedures so that theyacquire expertise and make the procedure-related mortality as low as in the West.However, since the treatment is expensive, the choice of diseases for which thisprocedure is carried out must be based on a careful analysis of the possible benefit.

REFERENCESRizzoJD. New summary slides show current trends in BMT.Autologous Blood and Marrow Transplant Registry:ABMTR Newsletter 1998;5:4-10.

2 Smith TJ, Hillner BE, Schmitz N, Linch DC, Dreger P, Goldstone AH, et al. Economic analysis of a randomizedclinical trial to compare filgrastim-mobilized peripheral-blood-progenitor-cell transplantation and autologousbone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma. J c/in Oneol 1997; IS:5-10.

3 Allieri MA, Lopez M, Douay L, Mary JY, NGuyen L, Gorin NC. Clonogenic leukemic progenitor cells in acutemyelocytic leukemia are highly sensiti ve to cryopreservation: Possible purging effect for autologous bone marrowtransplantation. Bone Marrow Transplant 1991;7:101.

4 Rizzoli Y, Mangoni L, Carella AM, Coleselli P, Angrilli F, Alessandrino EP,et al. Purging procedures for acuteleukemias in autologous BMT. Bone Marrow Transplant 1989;4:77-80.

5 Shpall EJ, Jones RB, Bearman Sl, Franklin W A, Archer PG, Curiel T, et al. Transplantation of enriched CD34-positive autologous bone marrow into breast cancer patients following high dose chemotherapy: Influence ofCD34-positive peripheral blood progenitors and growth factors on engraftment. J c/in Oneol 1994;12:28-36.

6 Rizzoli V, Mangoni L, Carlo-Stella C, Carella AM, Coser P, Angrilli F, et al. Autologous bone marrow trans-plantation in first remission acute myeloid leukemia using marrow purged with mafosfamide. Bone MarrowTransplant 1991;7 (SuppI2):37.

7 Johnston U, Homing SJ. Autologous hematopoietic cell transplantation in non-Hodgkin's lymphoma. HematolOneol c/in North Am 1999;13:889-918.

8 Siegel OS, Jagannath S, Desikan KR. Feasibility of high dose chemotherapy with peripheral blood stem cellsupport for multiple myeloma patients over the age of 70. Blood 1996;88 (Suppl I): 130a.

9 Ravindranath Y, Yaeger AM, Chang MN, StenberCP, Krischer J, Graham-Pole J,et 01. Autologous bone marrowtransplantation versus intensive consolidation chemotherapy for acute myeloid leukaemia in childhood. PediatricOncology Group. N Engl J Med 1996;334:1428-34.

10 Harousseau JL, Cahn JY, Pignon B, Witz F, Milpied N, Delain M,etal. Comparison of autologous bone marrowtransplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukaemia. TheGroupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM). Blood 1997;90:2978-86.

II Zittoun RA, Mandelli F, Willenze R, Labar B, Resegotti L, Leoni F,et al. Autologous or allogeneic bone marrowtransplantation compared with intensive chemotherapy in acute myelogenous leukaemia. European Organizationfor Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maliguesdell' Adulto (GIMEMA) Leukaemia Cooperative Groups. N Engl J Med 1995;332:217-23.

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14 Rodriguez-Monge EJ, Cabanillas F. Long-term follow-up of platinum-based lymphoma salvage regimens. TheM.D. Anderson Cancer Center Experience. Hematol Oneol CUn North Am 1997;11:937-47.

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marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 1987;316:1493-8.

16 Chopra R, McMillan AK, Linch DC, Yuklea S, Taghipour G, Pearce R, et 01. The place of high-dose BEAMtherapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease: A single-center eight-yearstudy of 155 patients. Blood 1993;81:1137-45.

17 Attal M, Harousseau I, Stoppa AM, Sotto JJ, Fuzibet IG, Rossi IF, et a/. A prospective, randomized trial ofautologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996;335:91-7.

18 Alexanian R, Dimopoulos M, Smith T, Delasalle K, Barlogie B, Champlin R. Limited value of myeloablativetherapy for late multiple myeloma. Blood 1994;83:512-16.

19 Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D,etal. Total therapy with tandem transplantsfor newly diagnosed multiple myeloma. Blood 1999;93:55--65.

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MAMMEN CHANDY

Department of HaematologyChristian Medical College Hospital

VelloreTamil Nadu

-Editor

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