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Whither the Bone Marrow Transplantation in Multiple Myeloma?

February 2018
Acta Haematologica 139(2):131-131

February 2018
139(2):131-131

Authors:

Clinica Ruiz

Received: November 06, 2017 Accepted: January 23, 2018 Published online: February 14, 2018 Issue release date: Published online first

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Editorial Comment

Acta Haematol 2018;139:131–131

Whither the Bone Marrow

Transplantation in Multiple Myeloma?

Guillermo J. Ruiz-Argüelles

Centro de Hematología y Medicina Interna, Clínica Ruiz, Puebla, Mexico

Received: November 6, 2017

Accepted after revision: January 23, 2018

Published online: February 14, 2018

Guillermo J. Ruiz-Argüelles, MD, FRCP (Glasg), MACP, DSc (hc)

Centro de Hematología y Medicina Interna, Clinica Ruiz

8B Sur 3710

Puebla 72530 (Mexico)

E-Mail gruiz1 @ hsctmexico.com

E-Mail karger@karger.com

www.karger.com/aha

DOI: 10.1159/000487121

Bone marrow transplantation has become an accepted

and important medical intervention and a routine part of

medical practice. However, its utility in a number of dis-

eases has been questioned recently on the basis that there

are better nontransplant therapeutic options. The ques-

tion of whether these moves to eradicate bone marrow

transplantation as an option stem from purely scientific

reasons has been raised [1]. Front-line treatment of high-

dose melphalan and autologous stem cell transplantation

(ASCT) has improved the prognosis of patients with mul-

tiple myeloma (MM). We and others have shown that the

cost-benefit ratio of ASCT as front-line treatment for pa-

tients with MM is considerably better than that of front-

line treatment with novel antimyeloma drugs [2], and this

observation is particularly critical in underprivileged cir-

cumstances. On the other hand, the capability to carry out

ASCT procedures in MM on an outpatient basis has re-

sulted in substantial decreases in the cost of autografting

patients with this disease [3, 4]. The paper by Muta et al.

[5] in the last issue of Acta Haematologica supports the

role of ASCT as a salvage treatment for patients with re-

lapsed MM, in turn supporting the usefulness of this pro-

cedure in another setting of the disease.

In an era when research on the treatment of patients

with MM relies mainly and dangerously on the assess-

ment of novel, extremely expensive antimyeloma drugs

such as the new proteasome inhibitors, IMID and mono-

clonal antibodies, this type of refreshing paper is welcome

indeed; the benefit of the patients was and should always

be considered over other non-strictly scientific or ethical

reasons in therapeutic choices for individuals with MM

[6]. The observation made in a well-developed country

such as Japan might turn out to be even more useful in

circumstances of economic restraint.

References

1 Ruiz-Arguelles GJ: Whither the bone marrow

transplant. Hematology 2010; 15: 1–3.

2 López-Otero A, Ruiz-Delgado GJ, Ruiz-Ar-

güelles GJ: A simplified method for stem cell

autografting in multiple myeloma: a single

institution experience. Bone Marrow Trans-

plant 2009; 44: 715–719.

3 Karduss-Urueta A, Ruiz-Argüelles GJ, Perez

R, Ruiz-Delgado GJ, Cardona AM, Labastida-

Mercado N, Gómez LR, Galindo-Becerra S,

Reyes P, Alejo-Jiménez J: Cell-freezing devic-

es are not strictly needed to start an autolo-

gous hematopoietic transplantation program:

non-cryopreserved peripheral blood stem

cells can be used to restore hematopoiesis af-

ter high dose chemotherapy – a multicenter

experience in 268 autografts in patients with

multiple myeloma or lymphoma. Study on

behalf of the Latin-American Bone Marrow

Transplantation Group (LABMT). Blood

2014,124: 849.

4 Gale RP, Ruiz-Argüelles GJ: The big freeze

may be over. Bone Marrow Transplant, in

press.

5 Muta T, Miyamoto T, Kamimura T, Kanda Y,

Nohgawa M, Ueda Y, Iwato K, Sasaki O, Mori

T, Uchida N, Iida S, Fukuda T, Atsuta Y, Su-

nami K: Significance of salvage autologous

stem cell transplantation for relapsed multi-

ple myeloma: a nationwide retrospective

study in Japan. Acta Haematol 2018; 139: 35–

44.

6 Ruiz-Argüelles GJ, Steensma DP: Staunching

the rising costs of haematological health care.

Lancet Haematol 2016; 3: 10.

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Whither the bone marrow transplant?

Article

Full-text available

Feb 2010
HEMATOLOGY

Guillermo J Ruiz-Argüelles

Bone marrow transplantation (BMT) has become an accepted and important medical intervention which has become a routine part of medical practice. Its utility has, however, been questioned recently in a number of diseases in which its role has been clearly established on the basis that there are better non-transplant therapeutic options. The suspicion that these moves to eradicate BMT as an option may not stem from purely scientific reasons has prompted the preparation of these personal reflections. I will focus this discussion only on two diseases in which BMT has been shown to be useful: chronic myelogenous leukemia (CML) and multiple myeloma (MM).

A simplified method for stem cell autografting in multiple myeloma: A single institution experience

Article

Full-text available

May 2009

In a 14-year period in a single institution 31 autografts were performed in 26 patients with multiple myeloma (MM), using a simplified and affordable autografting procedure: conducting the grafts on an outpatient basis and avoiding stem cell freezing. Autografts were started on an outpatient basis in all instances, but four patients were admitted to the hospital. Median time to achieve more than 0.5 x 10(9)/l granulocytes was 27 days, whereas median time to recover above 20 x 10(9)/l plts was 37 days. CR was achieved in 19 cases and a very good partial response in 6 cases. The 100-day mortality was 9.6%. The overall median post-transplant survival has not been reached, being above 76 months, whereas the 76-month survival is 80%. The median cost of each procedure was US$ 15 000. Survival results were substantially better than those of historical control in a group of patients treated in the same institution with melphalan/prednisone. It is concluded that high-dose therapy rescued with a simplified autologous stem cell graft is a valid, useful and affordable therapeutic option for patients with MM, even with economical restraints.

Cell-Freezing Devices Are Not Strictly Needed to Start an Autologous Hematopoietic Transplantation Program: Non-Cryopreserved Peripheral Blood Stem Cells Can be Used to Restore Hematopoiesis after High Dose Chemotherapy: A Multicenter Experience in 268 Autografts in Patients with Multiple Myeloma or Lymphoma. Study on Behalf of the Latin-American Bone Marrow Transplantation Group (LABMT)

Article

Dec 2014

Storage of peripheral blood stem cells (PBSC) at 4ºC is a simple and inexpensive alternative to cryopreservation for preserving the clonogenic capacity of progenitors cells in the autologous transplant setting, however it has been perceived as unsafe and has deserved little attention. We present the experience of two Latin-American centers using refrigerated, non-cryopreserved stem cells after conditioning with high dose melphalan, CBV or BEAM in a large group of lymphoma and myeloma patients Materials and Methods PBSC were mobilized with filgrastim 5 mg/kg/BID for three to six days.One to three apheresis procedure were employed; the cells were stored at 4ºC for 5 to 6 days in patients who received BEAM or CBV and for 3 days in those given melphalan. All of the conditioning regimens were administered preserving the full intensity of dose (Table 1). After the autograft all patients received filgrastim or pegfilgrastim Table 1 BEAM D-5 D-4 D-3 D-2 D-1 BiCNU 300 mgs/m2 X Etoposide 200-400 mgs/m2 X X X X Citarabine 300-400 mgs/m2 X X X Melphalan 140 mgs/m2 X CBV BiCNU 300 mgs/m2 13 patients received carboplatin 900 mgs/m2 instead BiCNU X Etoposide 300 mgs/m2 X X X Ciclophosphamide 2.000 mgs/m2 X X X Melphalan Melphalan 200 mgs/m2 X Melphalan 100 mgs/m2 X X Results 102 lymphoma patients: 48 Hodgkin`s lymphoma (HL) and 54 non-Hodgkin´s lymphoma (NHL) received BEAM (71) or CBV (31). A median of 3.3 millions/kg of CD34 was infused; the median viability of the cells after 5-6 days of refrigeration (trypan blue exclusion) was 82%. 101 out of 102 patients engrafted, median time to achieve 500/ul neutrophil or more was 12 days, 100 were evaluable for thrombopoiesis, 99 of them had a self- sustained platelet count of 20.000 or more at a median of 17 days. The OS at 5 years was 59% and 42% for patients with Hodgkin and lymphoma respectively 151 patients with multiple myeloma received melphalan 200 mgs/m2. After 72 hours of refrigeration, a median of 2.6 millions/kg of CD34 cells were infused, the viability in all cases being > 90%. Three patients were not evaluable because early death. Median time to achieve 500 neutrophil or more and 20.000 platelets was 12 (9-50) and 15 (7-50) days. The OS at 5 years was 50% 21 patients with NHL and HL received as conditioning regimen melphalan 200 mgs/m2. After 72 hours of storage, a median of 1.75 millions/kg of CD34 cells were transplanted, 100% of them engrafted, median time to 500 neutrophils and 20.000 platelets was 11.9 and 15 days respectively There were no cases of secondary engraftment failure in any of the three groups Conclusion In this series of 268 patients, we have shown that autologous PBSC can be kept at 4ºC in a conventional blood bank refrigerator for up to six days and use them to rescue high-dose chemotherapy in both multiple myeloma and lymphoma patients. Avoiding freezing procedures results in substantial cost savings. The availability of freezing devices for hematopoietic stem cells is not anymore an obstacle to start a an autologous transplantation program This observation is critical in areas of underprivileged economic circumstances, where more than 50% of the inhabitants of the world live. Disclosures No relevant conflicts of interest to declare.

Significance of Salvage Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma: A Nationwide Retrospective Study in Japan

Article

Jan 2018

Autologous stem cell transplantation (ASCT) has been employed for patients with relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective study aimed to examine the survival benefit from salvage ASCT. Among 446 patients with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT, the employment of which reduced the risk of mortality after relapse (p = 0.041). Using the parameters before initial ASCT, the advantage of salvage ASCT compared to standard therapy was confirmed in the subgroup with an international staging system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also confirmed in the subgroup excluding those with early relapse within 7 months after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a favorable prognosis is apparent for those with a time to relapse after initial ASCT of longer than 24 months. The overall survival after salvage ASCT was favorable excluding patients with the following factors: early relapse, poor PS, moderate/severe renal comorbidity, and progressive disease (p < 0.001). In conclusion, our results reinforced the evidence for encouraging salvage ASCT for eligible patients.

Staunching the rising costs of haematological health care

Article

Oct 2016

The big freeze may be over

Rp Gale
Gj Ruiz-Argüelles

Gale RP, Ruiz-Argüelles GJ: The big freeze may be over. Bone Marrow Transplant, in press.

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Jan 2016
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Gj Ruiz-Argüelles
Dp Steensma

Ruiz-Argüelles GJ, Steensma DP: Staunching the rising costs of haematological health care. Lancet Haematol 2016; 3: 10. Downloaded by: Univ. of California Santa Barbara 128.111.121.42-2/15/2018 3:35:41 PM