Highligts Tandem Meetings 2018 Neoplasias mieloproliferativas£o Regional... · 3 DIPSS Low risk...

Highligts Tandem Meetings 2018 – Neoplasias mieloproliferativas

Prof. Dra. Vaneuza A.M.Funke

Responsavel Técnico STMO Adulto

HC-UFPR

JAK Inhibitors Prior to Allogeneic Stem Cell

Transplant for Patients with Myelofibrosis: A

Prospective Study

Methods:

• single center phase II prospective study of JAK inhibitor

therapy followed by myeloablative or reduced intensity HCT

in 22 patients with primary (n = 15) and secondary (n = 7)

MF.

• Patients were given a JAK inhibitor for at least 8 weeks

(median 7.5 months; range 2 - 30 months) prior to HCT,

which was tapered over 1-2 weeks through Day - 4 of

conditioning.

Salit R et al (FHCRC)



Prospective Study


Patients Charachteristics N=22

Primary MF

Secondary MF

15

7

Conditioning

Flu-Mel

BuCy

3

19

Donor

Related

Unrelated

DCB

14

5

3

DIPSS

Low risk

Intermediate I

Intermediate II

1

7

14

Results N=22

Engraftment 22

GVHD

Acute

II-IV

III-IV

Chronic

Severe

13

2

4

1

Relapse 2

DIPSS

Intermediate I

Intermediate II

2

20

NRM 2

2yOS 89%



Prospective Study


Results:

• All patients engrafted at a median of 18 (range 14-27) days. There were

no graft failures and no incidences of cytokine release syndrome.

• Median day 80 chimerism was 88% CD3 and 100% CD33

• At a median follow up of 16.9 months, 20 of the 22 patients are alive

for a 2 year survival of 89%.



Prospective Study

Conclusions:

• JAK inhibitor therapy pre-HCT is safe and the strategy of

overlapping a JAK inhibitor with conditioning chemotherapy

prevented cytokine release syndrome.

• Survival at 2-years in this cohort is 89% compared with 54% in

our closely matched historical cohort of intermediate-2 patients

who did not receive a pre-transplant JAK inhibitor.

• Both Grades III-IV acute and severe chronic GVHD were

encouragingly infrequent.



Prospective Study

Immunosuppression Withdrawal

Is an Effective Treatment of Relapse after

Allogeneic Stem Cell Transplant for Myelofibrosis

• January 2005 and July 2015; 92 patients with primary or secondary MF who

underwent first allo-SCT at MDACC.

• All patients with disease relapse (morphologic and/or molecular) or MM

(defined as less than 95% of donor cells origin) and who had

immunosuppression reduction/withdrawal as primary therapeutic

intervention were included.

• A total of 25 patients with a median age of 59 years were eligible for the final

analysis.

• All patients were on tacrolimus as their primary GVHD prophylaxis, but none

had active GVHD at time of relapse.

• Median time from allo-SCT to relapse/MM was 106 days (31-349) and

median time from relapse to immunotherapy reduction was 11 days (0-76).

• None of the patients received additional simultaneous treatment.

Samer A. Srour, et al

• 48% (12 of 25) responded to tacrolimus reduction as primary intervention

and achieved CR (MM, n=6; molecular/morphologic relapse, n=6).

• Among the responders, 3 died of GVHD complications and 9 remain alive

requiring no subsequent treatment.

• All responders developed GVHD, with liver GVHD universal to all patients

(100%).

• Tacrolimus was resumed (or dose increased) in all patients, and systemic

steroids ± photophoresis were used in 7 patients, with no notable negative

impact on graft-versus-tumor (GVT) effects.





• Among the non-responders (n=13; MM, n=6; molecular/morphologic

relapse, n=7), 8 died (6 of persistent/recurrent disease, and 2 of GVHD) and

5 remain alive at last follow-up. Of these 5 patients, 4 had a second allo-SCT

and one patient received DLI.

• Only 4 (31%) of the nonresponding patients developed GVHD.

• With a median follow up of 52 months, the median OS was not reached for

all patients and the 5-year OS rates were 73% and 37% among responders

to tacrolimus withdrawal versus the nonresponders, respectively (Figure).








Views on Bone Marrow Transplant: A Survey of

Patients with Myelofibrosis

Methods:

• A survey for MPN patients was posted on multiple websites, including MPN Forum, MPN

Advocacy, MPN Research Foundation, and MPN Education foundation.

Results:

• There were 366 respondents. 129 patients indicated that they had MF: 62 had primary MF (PMF),

and 67 had secondary MF.

• Median age of respondents was 61 (31-84), and 80 (62%) were female.

• The majority identified themselves as “white” 125 (97%). 118 (91%) patients had at least some

college, 63 (49%) of patients indicated they had private insurance, and 45 (35%) had

medicare/medicaid. 65 (50%) are currently receiving ruxolitinib.

• Of these patients 49 (41%) had been referred for a bone marrow transplant consult, 41 of those

patients went to the consult. The majority of the patients felt that they received the information

they needed at the consult (n=35, 85%).

• 10 (25%) of patients plan to undergo a transplant in the near future, 6 (15%) at some point in the

future, and 24 (60%) do not plan on undergoing a transplant.

• Of those who were not going to transplant, there were a variety of concerns expressed (Table

1). Of the 16 patients who planned on proceeding with transplant, 14 provided reasons including

the belief that it will improve survival, the desire to be around for family, and fear of dying.

Jeanne Palmer et al

Concern Not important Important*

Worried about the financial impact it will have on my family 13 11

Worried about the financial impact it will have on me 12 12

I do not want my family to have to take care of me 10 14

I do not want to get sick 6 18

I would rather enjoy the time I have left 5 19

I do not want to spend a long time in the hospital setting during the

transplant

5 18

I do not believe it will dramatically improve my life expectancy 4 20

I feel my quality of life will be worse with transplant 3 21

I am worried about graft versus host disease 2 22

I am worried about dying from the transplant 2 22

Views on Bone Marrow Transplant: A Survey of

Patients with Myelofibrosis

Transplant Outcomes for Patients with Secondary Acute Myeloid Leukemia

(AML) Arising from Myeloproliferative Neoplasms (MPN).

METHODS

• All patients with AML arising from MPN who underwent SCT at

MD Anderson Cancer Center (Jan 2001-Feb 2017) were

included.

• 54 patients that underwent SCT, 5 underwent SCT twice. Only

the data for the first SCT was included. Patients receiving cord

blood or haploidentical SCT (n=11) were excluded. Finally, 43

unique SCT events were included in the study.

Mithun Vinod Shah,et al

Characteristics Value (N=43)

Age in years, median (range) 59 (14-72)

Sex, N (%)

Female

Male

12 (28)

31 (72)

Pre-SCT % blasts, median (range)

Bone marrow

Peripheral

5 (0-86)

1.5 (0-68)

Pre-SCT line of chemotherapy, median (range) 1 (0-5)

Donor Type, N (%)

Matched related

Matched unrelated

17 (40)

26 (60)

Cell Source, N (%)

BM

PB

9 (21)

34 (79)

HCT-CI, median (range)

≤4

>4

4 (0-11)

29 (67)

14 (33)

Melphalan in conditioning regimen, N (%)

Yes

No

14 (33)

29 (67)

Pre SCT, N (%)

7+3

Ara-C

JAK2i

HMA

29 (67)

7 (16)

9 (21)

10 (23)

Treatment with JAK2i/HMA pre-SCT, N (%)

No/ No

Yes / No

No / Yes

Yes / Yes

31 (72)

2 (5)

3 (7)



RESULTS

• Four (9.3%) patients had early death, and 38 (88.4%) patients

engrafted.

• Twenty eight patients died with AML recurrence being the most

common cause of death (n=17, 61%).

• The median follow up in patients alive was 41 months (5-170).

• The median PFS and OS were 6 and 15 months respectively.

• At 4 years:

• PFS: 31%,

• OS:38%

• Non-relapse mortality:24%

• Progression:43%

Mithun Vinod Shah,et al



RESULTS

The factors predicting reduced risk of progression on multivariate

analysis were:

• matched unrelated donors (vs. sibling donors, hazard ratio (HR)

0.36, p=0.03)

• and the inclusion of melphalan in conditioning regimen (vs. no

melphalan, HR 0.2, p=0.01).

• There was a trend for improved PFS at 1-year (HR

0.3, p=0.08, Figure 1) for those treated with JAK2i+HMA pre-

SCT.

• Acute graft-vs-host disease (GVHD) : 19 (46%) of 41 evaluable

patients

• Chronic GVHD :16 (44%) of 35 evaluable patients.Mithun Vinod Shah,et al





Haploidentical Transplantation Outcomes for

Secondary Acute Myeloid Leukemia –

on Behalf of the ALWP of the EBMT

• 166 pts with sAML who received Haplo-HCT between 2006-2016 (prior

MDS/MPN=128; OMHD=15; solid tumor=17; BMFS=6) were studied.

• Median age at Haplo-HCT was 60 years and time from diagnosis to Haplo-HCT 5

months.

• Median follow-up of surviving pts was 24 months. At transplantation, 77 pts were in

CR1 while 89 had active disease.

• 63 pts received ablative (MAC) and 103 reduced-intensity conditioning (RIC)

regimen.

• MAC conditioning was mostly with thiotepa, busulfan, and fludarabine (TBF) in 34

pts (54%) and RIC with TBF and fludarabine-TBI in 28 (27%) and 35 (34%) pts,

respectively.

• 35 pts received ATG, 119 received post-transplant cyclophosphamide (PTCy), and

12 received both.

.

Zhuoyan Li, et al

Haploidentical Transplantation Outcomes for Secondary Acute Myeloid Leukemia – on Behalf of the ALWP of the EBMT-

• Myeloid engraftment was achieved in 146 (88%) pts.

• 39 (25%) developed acute GVHD (grade II-IV) by day 100.

• The 2-year cumulative incidence of chronic GVHD: 25.5% , relapse

(RI): 30.3% and non-relapse mortality (NRM): 33.3%.

• 2 y Overall survival (OS): 42.5%, leukemia free survival (LFS):

36.4% and GVHD-free/relapse free survival (GRFS) 28.3%.

• Multivariate analysis:

• Active disease resulted in higher RI and inferior LFS, OS, and

GRFS compared with patients in CR1 at time of Haplo-HCT.

• PTCy was associated with lower NRM and superior LFS, OS,

and GRFS compared to ATG (HR 2.25, 2.01, 2.16, and 1.73,

respectively with p values <0.05; Figure 1) and a trend for

higher RI (HR=2.02, p=0.052).

Zhuoyan Li, et al

Haploidentical Transplantation Outcomes for

Secondary Acute Myeloid Leukemia –

on Behalf of the ALWP of the EBMT

Hematopoietic stem cell

transplantation in myelofibrosis: a

comparison between myeloablative and

reduced intensity conditioning

Funke VAM; Furtado VF; Santos GR; Sinamura LA;

Fagundes T; Nunes EC; Sola CB; Medeiros LA;

Pasquini R; Malvezzi M

Asbmt 2012

Instituições Participantes

• UFPR

• HNSG

• JAU

• INCA

• UFMG

• UNICAMP

• Einstein

• UFRGS

• USP-RP

TCTH para mielofibrose: experiência brasileira

Características dos pacientes (N=52)

Idade (Med) 46 (10-64)

Sexo

Masc

Fem

31

21

Doador

ap

nap

44 (1 haplo)

08

Fonte de células

Sp

MO

27

25


Características dos pacientes (N=52)

Tranfusões

>15

<15

16

32

Baço

>10 cm

<10cm

09

35

Cariótipo

Normal

ACA

27

08

N=52

Condicionamento

MA

RIC

27

25

Falha de Pega (%) 2%

DECH-A (%)

DECH-C (%)

SG 496,5 (11-4945)


Sobrevida Global

0 2 0 0 0 4 0 0 0 6 0 0 0

0

2 0

4 0

6 0

8 0

1 0 0

T im e

Pe

rc

en

t s

urv

iva

l

Sobrevida x Número de transfusões

0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0

0

2 0

4 0

6 0

8 0

1 0 0

D a y s

Pe

rc

en

t s

urv

iva

l

< 1 5

> 1 50.0269

Tipo de doador

0 2 0 0 0 4 0 0 0 6 0 0 0

0

2 0

4 0

6 0

8 0

1 0 0

S u rv iva l

Pe

rc

en

t s

urv

iva

l

a p

n a

0.0057

Sobrevida x esplenomegalia

P= 0,0187

0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0

0

2 0

4 0

6 0

8 0

1 0 0

S u rv iva l

Pe

rc

en

t s

urv

iva

l

b a c o < 2 0

B a c o > 2 0

Irradiacao esplenica como parte do condicionamento de

pacientes com Mielofibrose submetidos a HSCT

•Vaneuza A.M. Funke (Resp. Técnico STMO Adulto UFPR)

•Nelson Hamerschlak ( Hospital Albert Einstein)

•Mary Evelyn Flowers (FHCRC)

Proposta

• Estudo Piloto

• N= 10

• Endpoint primario : pega do enxerto

• Cond : Flu 150+ Bu 10-16 + ATG

• CTP

• Irradiacao esplenica 4 Gy -8 e -7

Agradecimentos

• Marco Bitencourt

• Daniela Setubal

• Caroline Bonamin

• Michel Oliveira

• Samir Nabhan

• Ricardo Pasquini

Date post:	03-Dec-2018
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