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At-home allo-HSCT program | Hospital Clinic of Barcelona

Feb 5, 2020

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is used in the treatment of hematological malignancies. In recent years, the demand for hospital beds in transplant units has increased owing to the development of alternative transplant methods, such as haploidentical (haplo) transplant with post-transplant cyclophosphamide (PTCy), reduced intensity conditioning (RIC) for elderly patients and the advent of chimeric antigen receptor (CAR) T-cell therapies.

However, there are several complications arising from allo-HSCT which make performing such transplants outside of the hospital setting challenging. These include graft- versus-host disease (GvHD), acute renal failure (ARF), and infectious events such as aspergillosis. Another concern with at-home allo-HSCT is the readmission rate. Despite this, at-home transplant programs have the potential to improve patient quality-of-life and reduce costs — if the benefits can be maintained and readmission rates reduced. To further assess the feasibility of an at-home approach, Gonzalo Gutiérrez-Garcia, Hospital Clinic of Barcelona, Barcelona, ES, and colleagues established an at-home allo-HSCT program and evaluated it for safety, convenience, and cost-effectiveness.

Study design

Between 2015 and 2018, 252 consecutive patients underwent allo-HSCT at Hospital Clinic of Barcelona. Of these, 41 were treated in the at-home modality, and they were compared to 39 patients who received transplants in an inpatient setting, matched by age, diagnosis, donor, conditioning, and GvHD prophylaxis. The only exclusion criteria were a history of alloimmunization to platelets and platelet transfusion refractoriness. The study aims were to analyze safety and feasibility of an at-home approach, the capacity to release beds for other programs, and economic efficiency.

Patient characteristics

  • Median age, years: 53 (range, 19–70)
  • All types of conditioning and donors were included ( Table 1)
  • Patients treated at-home had:
    • an Eastern Cooperative Oncology Group (ECOG) score 0–2
    • travel time from home to hospital <1 hour
    • a caregiver available 24 hours/day
    • signed patient acceptance
  • Conditioning regimen was myeloablative (MAC) for all patients except patients aged >55 years or those who had previously received an autologous stem cell transplant, who received a RIC regimen
  • The most commonly used GvHD prophylaxis regimens are shown in Table 1but varied depending on donor type:
    • For patients with sibling donors:
      • MAC: calcineurin inhibitor + tacrolimus + methotrexate
      • RIC: tacrolimus + mycophenolate mofetil (MMF)
    • For patients with matched unrelated donor (MUD), mismatched unrelated donor (MMUD) or haplo donors: high-dose PTCy + tacrolimus + MMF (for haplo donors only)
  • There were no significant differences in patient characteristics between groups

Table 1.Patient characteristics and transplant regimens by transplant modality

Characteristic or treatment

Inpatient (n= 39)

At-home (n= 41)

Age, years (range)

53 (45–60)

53 (45–53)

Diagnosis

AML, %

51

34

Lymphoma, %

10

20

MM, %

8

7

Disease status: CR vsPR vsSD, %

74 vs13 vs13

75.5 vs19.5 vs5

Donor: sibling vsMUD/MMUD vshaploidentical, %

49 vs49 vs2

34 vs63 vs2

Conditioning chemotherapy, %

Fludarabine and busulfan

85

85

Busulfan and cyclophosphamide

10

5

Others

5

10

GvHD prophylaxis, %

Tacrolimus + MMF

59

63

PTCy + tacrolimus

31

32

Tacrolimus + MTX

10

5

AML, acute myeloid leukemia; CR, complete response; MM, multiple myeloma; MMF, mycophenolate mofetil; MMUD, mismatched unrelated donor; MTX, methotrexate; MUD, matched unrelated donor; PR, partial response; PTCy, post-transplant cyclophosphamide; SD, stable disease

Protocol: at-home

  • Provision of seven clinical nurses, available from 08:00–22:00, in two shifts, seven days per week, and one hematologist, available eight hours per day 5 days per week. Outside of these times, the hematologist on duty at the hospital is in charge
  • Patients received conditioning and stem cell infusion (SCI) in the hospital
  • Patients were discharged one day post-SCI (Day +1) or the day after PTCy (Day +5)
  • For the following days, an at-home nurse cared for the patient for 2–3 hours/day and called each morning and evening. Afternoon sessions were arranged if necessary
  • The hematologist and nurse had at least two meetings to discuss patient status each day
  • If adverse events (AEs) were reported, the hematologist met the patient at the hospital
  • Follow-up was complete once engraftment was achieved
  • Table 2shows the main differences in the supportive measures between approaches

Table 2.Differences in supportive measures between at-home and inpatient care

 

At-home support

Inpatient support

Physical examination

At home by nurse

In hospital by physician

Monitoring vital signs

At home by nurse

In hospital

Blood samples taken

At home by nurse

In hospital

Platelet transfusion

At home by nurse

In hospital

Infusion of medication

At home by nurse

In hospital

Red blood cell transfusion

In hospital

In hospital

Prophylaxis infectious regimen

Levofloxacin, ceftriaxone, or ertapenem. Inhaled amphotericin-B + fluconazole, or posaconazole

Levofloxacin and fluconazole

Febrile neutropenia treatment

At home

In hospital

Other measures

Oral hydration (2L/day) + continuous IV infusion of normal saline (1L) + magnesium (3g/day).

Tacrolimus +/or MMF orally

Tacrolimus and/or MMF IV

Isolation measures

Single bedroom and protective reverse isolation and daily stroll with FFP3 mask outside

HEPA room with positive pressure, daily stroll with FFP3 mask within the hospital

HEPA, high-efficiency particulate air; IV, intravenous; MMF, mycophenolate mofetil

Results

  • In the at-home group, 93% were discharged on Day 1 post-SCI or PTCy prophylaxis
  • The readmission rate in the at-home group was 7%
  • Patients treated at home experienced significantly less febrile neutropenia and had a lower isolated bacteria distribution ( Table 3). There was no difference between 100-day readmission rate or rate of ARF

Table 3.Differences in infectious complications and AEs

 

At-home

Inpatient

P value

Febrile neutropenia, %

32

90

<0.0001

Isolated bacteria distribution, %

17

39

0.03

Aspergillosis, %

1

3

0.5

ARF, %

68

62

0.5

100-day readmission rate, %

22

26

0.7

AE, adverse event; ARF, acute renal failure

Bold font indicates significant values

  • There were no differences in one-year transplant related mortality (TRM), relapse incidence, or overall survival (OS) observed between groups, as shown in Table 4.
  • Main causes of death in patients treated at home: GvHD (n= 4), relapse (n= 4), resistant cytomegalovirus infection (n= 1), relapse of previous melanoma (n= 1), and pulmonary embolism (n= 1)
  • However, one-year acute GvHD (aGvHD) Grades III–IV was significantly lower in the at-home group

Table 4.GvHD rates, TRM, relapse, and OS rates

 

Total

At-home

Inpatient

P value

One-year aGvHD Grade I–II, %

51

58

43

0.2

One-year aGvHD Grade III–IV, %

19

10

29

0.03

One-year TRM, %

23

20

26

0.5

One-year CI of relapse, %

7

11

3

0.2

Two-year OS, %

71

69

71

0.87

aGvHD, acute graft-versus-host disease; CI, cumulative incidence; cGvHD, chronic graft-versus-host disease; TRM, transplant related mortality

The authors hypothesize that the reduction in severe aGvHD could be due to:

  • Higher stress in the inpatient environment leading to higher levels of inflammatory cytokines, potentially triggering aGvHD
  • Nutritional empowerment in the at-home group enhancing gut microbiota, decreasing the incidence of aGvHD

Cost analysis and hospital capacity

  • Savings from at-home allo-HSCT predominantly came from lower hospitalization charges
  • Median days saved from admission in at-home group: 23.5 days (range, 10–37)
  • Group costs were significantly higher in the inpatient setting
    • Inpatient vsat home: €79,888 vs€70,801, p= 0.01
  • Pharmacy costs were significantly higher in the at-home setting compared to the inpatient setting (€298 vs€255, p= 0.03)
  • At-home allo-HSCT increased capacity by 10.5 allo-HSCTs per year

Conclusion

At-home allo-HSCT was found to reduce the rates of febrile neutropenia and severe aGvHD, resulting in less hospital readmission. This approach was safe in relation to incidence of ARF, invasive aspergillosis infection, TRM, relapse, and mortality. Additionally, at-home allo-HSTC was also shown to be cost-effective.

As of the publication date, Hospital Clinic of Barcelona was able to treat twenty patients in their CAR T program without needing to provide additional resources, since hospital beds had been released by the at-home transplant program. The authors believe that their model is reproducible and can be implemented in other hospitals.

  1. Gutiérrez-Garcia G. et al.A reproducible and safe at-home allogeneic haematopoietic cell transplant program: first experience in Central and Southern Europe . Bone Marrow Transpl.2020 Jan 13. DOI: 10.1038/s41409-019-0768-x