High dose melphalan is an adequate preparative regimen for autologous hematopoietic stem cell transplantation in relapsed/refractory lymphoma

Figures & data

Table 1. Summary of the conditioning regimens employed in the autografts.

HD-Mel
Drug	Dose	Days
Melphalan	200 mg/m^2	−1
G-CSF	10 µg/kg	−5 to −1
BEAM-like combinations
Regimen 1
Drug	Dose	Days
Etoposide	300 mg/m^2	−3 to −1
Cyclophosphamide	50 mg/kg	−3 to −1
G-CSF	10 µg/kg	−5 to −2
Regimen 2
Drug	Dose	Days
Melphalan	100 mg/m^2	−2 and −1
Cyclophosphamide	600 mg/kg	−2 and −1
G-CSF	10 µg/kg	−5 to −2
Regimen 3
Drug	Dose	Days
Melphalan	100 mg/m^2	−2 and −1
Etoposide	300 mg/m^2	−2 and −1
G-CSF	10 µg/kg	−5 to −2

G-CSF: granulocyte-colony stimulating factor.

Table 2. Salient features of the HD-Mel and BEAM-like groups.

			HD-Mel (n = 25)	BEAM-like (n = 25)	p
Sex (%)		Female	8 (32)	10 (40)	0.5
		Male	17 (68)	15 (60)
Age, years (IQR)			41 (26.5–48)	38 (29.5–53)	0.7
Lymphoma	Hodgkin	Nodular sclerosing	10	10	0.3
		Lymphocyte predominant	2	0
		Mixed cellularity	2	3
		Lymphocyte depleted	0	0
	Non-Hodgkin	T-cell lymphoblastic lymphoma	2	0	0.1
		Diffuse large B cell lymphoma	6	5
		Primary mediastinal B cell lymphoma	0	2
		Small-cell lymphoma	1	2
		Mantle cell lymphoma	1	4
		Other	2	1
Ann Arbor stage		I	1	0	0.09
		II	7	2
		III	6	4
		IV	11	19
Therapy prior to ASCT (%)		One line	6 (24)	7 (28)	*
		Two lines	13 (52)	18 (72)
		Three lines	6 (24)	0 (0)

ASCT: autologous hematopoietic stem cell transplantation; IQR: interquartile range; p: p-value of comparisons between groups; *Comparison was not carried out due to the absence of patients with three lines of therapy in BEAM-like group.

Figure 1. Overall survival (OS) comparison according to conditioning and main features. (A) OS of patients in the HD-Mel group according to response at ASCT (p 0.9). (B) OS patients in the BEAM-like group according to response at ASCT (p 0.4).

Table 3. Results of univariate and multivariate Cox-regression models for overall survival in patients transplanted with HD-Mel.

Overall survival		Univariate			Multivariate
		HR	95%CI	p	HR	95%CI	P
Female sex		0.9	0.1–5.0	0.9	1.1	0.1–7.6	0.8
Age	≤30 years	–	–	–	–	–	–
	>30–45 years	0.2	0.03–2.4	0.2	0.2	0.02–2.7	0.2
	>45 years	0.2	0.03–2.6	0.2	0.2	0.01–4.4	0.3
Bulky disease		6.5	1.1–36.7	0.03	6.8	0.4–80.5	0.1
Non-Hodgkin lymphoma		1.5	0.3–7.8	0.5	3.2	0.4–21.9	0.2
Refractory disease		1.0	0.2–5.3	0.9	1.3	0.1–10.1	0.7
ASCT after 2016		0.4	0.04–3.5	0.4	0.4	0.04–4.9	0.5

ASCT: autologous hematopoietic stem cell transplantation; HR: hazard ratio; 95%CI: 95% confidence interval; p: p-value. Multivariate analysis used age, sex, diagnosis and year of transplant as covariates.

Table 4. Results of univariate and multivariate Cox-regression models for event-free survival in patients transplanted with HD-Mel.

Event-free survival		Univariate			Multivariate
		HR	95%CI	p	HR	95%CI	p
Female sex		0.2	0.03–3.1	0.2	0.1	0.01–1.7	0.1
Age	≤30 years	–	–	–	–	–	–
	>30–45 years	0.7	0.1–3.8	0.7	0.5	0.09–2.7	0.4
	>45 years	0.4	0.07–2.9	0.4	1.3	0.09–17.9	0.8
Bulky disease		3.6	0.7–18.9	0.1	6.5	0.5–81.6	0.1
Non-Hodgkin lymphoma		1.3	0.3–5.4	0.6	2.6	0.4–14.5	0.2
Refractory disease		1.1	0.2–4.5	0.8	1.1	0.2–5.6	0.8
ASCT after 2016		0.4	0.08–2.2	0.3	0.2	0.02–1.6	0.1

ASCT: autologous hematopoietic stem cell transplantation; HR: hazard ratio; 95%CI: 95% confidence interval; p: p-value. Multivariate analysis used age, sex, diagnosis and year of transplant as covariates.

Figure 2. Comparison of overall survival (OS) and event-free survival (EFS) between HD-Mel and BEAM-like cohorts. (A) OS in patients treated with HD-Mel or BEAM-like, there were no significant differences (p 0.5); (B) Comparison of EFS in patients treated with HD-Mel or BEAM-like, there were no significant differences (p 0.5).

Figure 3. Event-free survival (EFS) comparison according to conditioning and main features. (A) EFS of patients in the HD-Mel group according to response at ASCT (p 0.8); (B) EFS of patients in the BEAM-like group according to response at ASCT (p 0.1).

Figure 4. Comparison of overall survival at two, three and five years (y) informed for different regimens. Data of this study and from the literature (ref).

Table 5. Costs of a 50 mg vial of melphalan, either innovator or generic (*) in different parts of the world.

Country	Price in US dollars
United States	Up to $ 2500
Spain	$ 67
Mexico (*)	$ 660
Colombia (*)	$ 100