Outcomes of patients after mobilization failure of hematopoietic stem cells for autologous stem cell transplantation

Santinelli-Pestana, Diego Vinicius; Chaer, Livia Netto; Mariano, Livia; Otuyama, Leonardo Jun; Medrone Junior, Alfredo; Rocha, Vanderson

doi:10.1016/j.htct.2023.04.006

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Hematology, Transfusion and Cell Therapy

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Sumário

Original article • Hematol., Transfus. Cell Ther. 46 (3) • 2024 • https://doi.org/10.1016/j.htct.2023.04.006 copy

Outcomes of patients after mobilization failure of hematopoietic stem cells for autologous stem cell transplantation

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction

Autologous hematopoietic stem cell transplantation (ASCT) is the long-term consolidation treatment for various hematological malignancies. The collection of hematopoietic stem cell yield is critical to successful ASCTs, but not always achieved due to hematopoietic stem cell mobilization failure (HSCMF). Details regarding the cell collection and outcomes of those who fail mobilization are still lacking. Therefore, this study aimed to yield data on clinical outcomes and cellular products after HSCMF.

Methods

Retrospective, unicentric study assessing clinical outcomes and characteristics of collected progenitor cells. The data were collected from patient databases. The results were reported in median, rates and percentages and absolute values. Patients older than 18 years of age at the time of mobilization and HSCMF were included.

Results

Five hundred ninety-nine patients underwent mobilization protocols. Thirty-five (5.8%) of them failed in the mobilization and fourteen (40%) died. Median time to death was eight months. Disease progression and infection were responsible for all deaths. Median relapse-free survival was 6.5 months (20 patients, 57%). Seven (20%) survivors were receiving salvage therapy and five (14%) were being followed clinically. Six (20.6%) participants underwent collection by apheresis, with insufficient cell collection. The median quantity of peripheral CD34+ cells in those patients was 10.5/mm³. The median CD34+ quantity collected was 0.86 × 10⁶ CD34+ cells/kg.

Conclusions

The mobilization failure was associated with limited survival. Nonetheless, collected products offered perspectives for ex vivo expansion. Further studies should investigate the feasibility of expanding collected CD34+ cells to use as grafts for ASCT.

Keywords
Hematopoietic stem cell mobilization failure; Autologous stem cell transplantation

Participant number	Disease	Peripheral (CD34+/mm³)	No. of Collections	Mobilization protocol	Total collected cells (x 10⁶ CD34+/kg)	Outcome
1*	DLBCNHL (CNS)	6.7	2	G-CSF + plerixafor	1.79	Alive chemo + RT + follow-up (last contacted 14 months after mobilization)
2	DLBCNHL	1.7	1	G-CSF + plerixafor	0.28	Death 11 months after mobilization
3*	AML	10.7	2	G-CSF	1.73	Alive chemo + follow- up (last contacted 24 months after mobilization)
4*	DLBCNHL	11.8	3	Chemo + G-CSF	0.42	Alive-lost follow-up. Returned to original health care institution (last assessment was 3 months after mobilization)
5	MM	10.3	1	G-CSF	0.72	Death 14 months after mobilization
6	MM	11.2	1	G-CSF	1.01	Alive Follow-up (last contacted 34 months after mobilization)

	Success (n = 564)	Failure (n = 6)
Baseline disease (frequency/percentage)
Gammopathies	284 (50.35%)	2 (33.33)
Hodgkin lymphoma	105 (18.62%)	0 (0%)
Non-Hodgkin lymphoma	147 (26.06%)	3 (50.00%)
AML	1 (0.18%)	1 (16.67%)
Solid tumor	26 (4.61%)	0 (0%)
APML	1 (0.18%)	0 (0%)
Total^* * Missing data were independently excluded from the report of each variable of interest, accounting for different values in the total number of observations reported for a given group. Patients who have not been subjected to collection were not reported in this table. Success = patients who successfully mobilized CD34+ cells; Failure = patients who failed to mobilize CD34+ cells, but underwent collection. G-CSF = granulocyte-colony stimulating factor; chemo = chemotherapy.	564 (100%)	6 (100%)
Clinical outcome
Alive	386 (68.44%)	1 (16.67%)
Deceased	130 (23.05%)	0 (0%)
Lost follow-up	48 (8.51%)	5 (83.33%)
Total^* * Missing data were independently excluded from the report of each variable of interest, accounting for different values in the total number of observations reported for a given group. Patients who have not been subjected to collection were not reported in this table. Success = patients who successfully mobilized CD34+ cells; Failure = patients who failed to mobilize CD34+ cells, but underwent collection. G-CSF = granulocyte-colony stimulating factor; chemo = chemotherapy.	564 (100%)	6 (100%)
Peripheral CD34+ cells (CD34+/mm3)
Minimum	1.4	1.7
Maximum	539.9	11.8
Median	27	10.5
Total^* * Missing data were independently excluded from the report of each variable of interest, accounting for different values in the total number of observations reported for a given group. Patients who have not been subjected to collection were not reported in this table. Success = patients who successfully mobilized CD34+ cells; Failure = patients who failed to mobilize CD34+ cells, but underwent collection. G-CSF = granulocyte-colony stimulating factor; chemo = chemotherapy.	349	6
Number of collections
Minimum	0	1
Maximum	5	3
Median	1	1.5
Protocol used in the first mobilization trial
G-CSF	264 (46.81%)	3 (50.00%)
G-CSF + chemo	286 (50.71%)	3 (50.00%)
G-CSF + plerixafor	12 (2.13%)	0 (0%)
G-CSF + chemo + plerixafor	2 (0.35%)	0 (0%)
Total^* * Missing data were independently excluded from the report of each variable of interest, accounting for different values in the total number of observations reported for a given group. Patients who have not been subjected to collection were not reported in this table. Success = patients who successfully mobilized CD34+ cells; Failure = patients who failed to mobilize CD34+ cells, but underwent collection. G-CSF = granulocyte-colony stimulating factor; chemo = chemotherapy.	564 (100%)	6 (100%)
Protocol used in the second mobilization trial
G-CSF	12 (17.39%)	0 (0%)
G-CSF + chemo	28 (40.58%)	1 (33.33%)
G-CSF + plerixafor	28 (40.58%)	2 (66.67%)
G-CSF + chemo + plerixafor	1 (1.45%)	0 (0%)
Total^* * Missing data were independently excluded from the report of each variable of interest, accounting for different values in the total number of observations reported for a given group. Patients who have not been subjected to collection were not reported in this table. Success = patients who successfully mobilized CD34+ cells; Failure = patients who failed to mobilize CD34+ cells, but underwent collection. G-CSF = granulocyte-colony stimulating factor; chemo = chemotherapy.	69 (100%)	3 (100%)
Protocol used in the third mobilization trial
G-CSF	2 (33.33%)	0 (0%)
G-CSF + chemo	3 (50.00%)	0 (0%)
G-CSF + plerixafor	1 (16.67%)	2 (100%)
Total^* * Missing data were independently excluded from the report of each variable of interest, accounting for different values in the total number of observations reported for a given group. Patients who have not been subjected to collection were not reported in this table. Success = patients who successfully mobilized CD34+ cells; Failure = patients who failed to mobilize CD34+ cells, but underwent collection. G-CSF = granulocyte-colony stimulating factor; chemo = chemotherapy.	6 (100%)	2 (100%)
Total collected cells (x 10⁶ CD34+/kg)
Minimum	2	0.28
Maximum	63.9	1.79
Median	4.89	0.86

Participant number	Disease	Processed blood volume (mL)	Minimum volume (mL)	Maximum volume (mL)	Median volume (mL)
1	Non-Hodgkin lymphoma	31,263	-	-	-
2	Non-Hodgkin lymphoma	15,897	-	-	-
3	AML	33,866	-	-	-
4	Non-Hodgkin lymphoma	54,653	-	-	-
5	MM	12,026	-	-	-
6	MM	14,196	-	-	-
Total = 6		-	12,026	54,653	23,580

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] * Corresponding author at: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP), Rua Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil. E-mail address:diego.pestana@fm.usp.br (D.V. Santinelli-Pestana)