Table 1 Characteristics of included studies and quality assessment results

Malpica

Leukemia & Lymphoma

Retrospective cohort

Six centers from four Latin American countries (Argentina, Chile, Colombia, and Peru)

57

1. AZT-IFN alone

2. Multi-agent chemotherapy alone

3. Combination chemotherapy and AZT-IFN

4. Single-agent chemotherapy and/or regional therapy

Acute n = 54; lymphomatous n = 84;

chronic n = 18;

smoldering n = 5

-No report of survival rate based on the type of regimen

Good

Malpica

JCO Global Oncology

Retrospective cohort

Eleven Latin American countries

57

1. AZT-IFN alone

2. Multi-agent chemotherapy alone

3. Combination chemotherapy and AZT-IFN

4. Single-agent chemotherapy and/or regional therapy

Acute n = 73; lymphomatous n = 122;

chronic n = 26;

smoldering n = 5

-In patients with aggressive ATLL who achieved complete response (CR), first-line treatment with AZT-IFN (alone or in combination with chemotherapy) showed better PFS compared to chemotherapy alone in acute ATLL.

-The differences in PFS between the treatment approaches were not statistically significant.

Good

Guery

Annals of Hematology

Retrospective cohort

France

51

1. Zidovudine-interferon alfa

2. Chemotherapy

Acute n = 23; lymphomatous n = 14;

chronic n = 8;

smoldering n = 2

-No report of survival rate based on the type of regimen.

Good

Nogueira

Blood

Ambispective observational study

Brazil

50

1. chemotherapy with anthracycline-based regimens

2. immunotherapy and antiviral therapy

Acute 29%; lymphomatous 46%;

chronic 17%;

smoldering 8%

-No report of survival rate based on the type of regimen.

Poor

Malpica

Blood

Retrospective cohort

USA

52

1. chemotherapy alone,

2. combined chemotherapy with AZT-IFN (concurrently or sequentially),

3. AZT-IFN alone.

Acute n = 80; lymphomatous n = 96;

chronic n = 5;

unfavorable chronic n = 7;

smoldering n = 3

-In patients with aggressive adult T-cell leukemia/lymphoma (ATLL) who achieved complete response (CR) after treatment, the median progression-free survival (PFS) was 48 months for those who received AZT-IFN.

-In contrast, patients who achieved CR after chemotherapy had a median PFS of 11 months.

-The difference in PFS between AZT-IFN and chemotherapy was statistically significant (p = 0.003).

Good

Oliveira

Brazilian Journal of Hematology and Hemotherapy

Retrospective cohort

Brazil

NR

1. first-line multiagent chemotherapy,

2. first-line antiviral therapy,

3. chemotherapy associated with antiviral therapy

Acute n = 16; lymphomatous n = 13;

chronic n = 23;

smoldering n = 26;

primary cutaneous tumoral n = 5

-Favorable chronic patients treated with antivirals had longer survival compared to the unfavorable subtype.

-In the case of the acute form of the disease, first-line chemotherapy showed better survival outcomes compared to antivirals, although the difference was not statistically significant.

Good

Zell

Oncotarget

Retrospective cohort

USA

54

1. Chemotherapy Only,

2. Chemotherapy with antiviral

Acute n = 36; lymphomatous n = 14;

chronic/smoldering n = 3

-There was no significant difference in survival between patients who received chemotherapy alone and those who received chemotherapy with antiviral agents.

Good

Cordeiro

Blood

Retrospective cohort

Brazil

49

1. Interferon alpha and zidovudine (IFN + AZT),

2. Polychemotherapy, usually with CHOEP regimen

Acute n = 15; lymphomatous n = 3;

chronic n = 6;

smoldering n = 5

-Patients with acute adult T-cell leukemia/lymphoma (ATLL) treated with chemotherapy as first-line therapy had a median overall survival (OS) of 5.8 months.

-This OS result is comparable to the average survival of 6 months reported in the literature for acute ATLL patients treated with chemotherapy.

-However, patients treated with first-line IFN + AZT (interferon + azidothymidine) had a longer average survival of 9 months compared to chemotherapy alone.

Fair

Pimentel

Retrovirology

Retrospective cohort

USA

NR

1. High-dose AZT/interferon (IFN) as first line therapy,

2. Chemotherapy-based regimens

Acute n = 51; lymphomatous n = 50;

chronic n = 5;

smoldering n = 2

-In the study, several long-sustained responses were observed in patients with acute and unfavorable chronic subtypes of the disease.

-These patients were treated with first-line AZT and IFN alone.

-These sustained responses translated into a survival benefit for the patients.

Fair

Hodson

Retrovirology

Case series

UK

52

First line treatment with zidovudine and interferon alpha (ZDV/IFN-a

Chronic n = 4

-All patients included in the study remained alive.

-The median overall survival for these patients was 64 months, with a range of 27 to 106 months.

Fair

Fields

Blood

Case series

UK

NR

1. Zidovudine (ZDV)/Interferon-a (IFN), anti-CD25/bortezomib;

2. ZDV/INF, anti-CD25/bortezomib, etoposide, Gemcitabine/Oxaloplatin;

3. Sodium valproate, ZDV/IFN, etoposide

Chronic n = 3

-No report of survival rate based on the type of regimen.

Poor

Kchour

Retrovirology

Retrospective cohort

Iran

NR

Arsenic/IFN/zidovudine

Acute n = 2; lymphomatous n = 2;

Chronic n = 12

-No report of survival rate based on the type of regimen.

Fair

Hodson

Journal of Clinical Oncology

Retrospective cohort

UK

58

1. chemotherapy only

2. Antiviral treatment administered concurrently with or immediately sequentially to first-line chemotherapy

3. Initial chemotherapy with antiviral treatment administered at any time after relapse

Acute n = 29; lymphomatous n = 44

-The use of ZDV (zidovudine) and IFN (interferon) at any time resulted in prolonged survival in acute and lymphoma subtypes of adult T-cell leukemia/lymphoma (ATLL).

-The use of ZDV/IFN was associated with a significant reduction in the risk of death in aggressive ATLL.

-The hazard ratio for the reduction in risk of death was 0.23, with a 95% confidence interval of 0.09 to 0.60.

-The use of ZDV/IFN in aggressive ATLL showed a significant association with improved survival (P = 0.002).

Good

Kchour

Leukemia & Lymphoma

Observational cohort

Iran

51

AZT/IFN

Acute n = 9; lymphomatous n = 5;

Chronic n = 14

-The study confirmed that treatment with AZT (azidothymidine) and IFN (interferon) induces a high response rate in patients.

-This treatment also resulted in prolonged survival.

-Importantly, the AZT/IFN treatment was associated with minimal side effects.

Fair

Hermine

The Hematology Journal

Phase II trial

France

NR

Arsenic/IFN/zidovudine

Acute n = 4; lymphomatous n = 3

-No report of survival rate based on the type of regimen.

Poor