Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients

Effect of Cell Harvesting Methods for Bone Marrow

Transplantation on Multiple Events among Myeloid
Leukemia Patients

Melvin Estolano (2159122)

Quynh Long Khuong (2159280)
Jessa Mae Lastimoso (2159120)
Jose Carlos Cortiñas Porras (2055631)

Presentation 4
14 December 2022

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Outline of the Presentation

Outline of the Presentation

▶ Introduction

▶ Methods

▶ Results and Discussion

▶ Conclusion

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Introduction

Introduction

▶ A clinical trial was conducted to evaluate the effects of two stem cell
harvesting methods: from pelvic bone (traditional method) vs. from
the peripheral blood (new method)

▶ Objective of this analysis: to compare the effect of two stem cell

harvesting methods on the time to three related events (cGVHD,
recurrence, and death) among leukemia patients

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Methodology

Study setting and participants (revisit)

▶ Participants: acute (AML) and chronic (CML) myeloid leukemia

patients undergoing BMT from related donor
▶ Comparing groups: two methods of stem cell harvesting
Traditional method: bone marrow of pelvic bone (BM)
New method: from the peripheral blood (PB)
▶ Sample size: 100 patients, 49 patients received BMT from PB and
51 received BM
▶ Outcomes: Time to first event
Leukemia recurrence
Symptoms of chronic graft-vs-host disease (cGVHD)
Death
▶ Covariates: patient’s age and disease types (AML/CML)
▶ Note: number of events for recurrence: 5; cGVHD: 86, and death: 5
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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Methodology

Competing risk

▶ Clinical perspective
Death is a competing risk of both recurrence and cGVHD
cGVHD reduces the risk of recurrence

▶ Study setting
Followed patients until first event occurred
Every event prevents the occurrence of other events

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Methodology

Statistical analysis
▶ The proportional sub-distribution hazard model (Fine and Gray, 1999)
was used
▶ Several diagnostic checking tools were utilized
The functional form of age via the Martingale residuals plot
Proportional hazards assumption via the plots of Scaled Schoenfeld
residuals versus time
Model goodness-of-fit via comparing cumulative incidence function
(CIF) corresponding to the PH model vs. CIF predicted
sub-distribution hazard model
▶ When the PH assumption is violated, time-varying fixed effects are
included (Scrucca, L et al, 2010)
▶ Analysis was conducted for each event separately
▶ Package cmprsk in R
▶ Significance level 5%
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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Results

Functional form of age

Figure 1: Functional form of age

Note: the functional form of age was checked from a cause-specific PH

models
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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Results

Model formulation

Proportional sub-distribution hazard model

′β
hj (t) = h0j (t)e Z

Where, Z = β1j age + β2j treatment + β3j diagnosis

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Results

Proportional hazards assumption

Figure 2: Scaled Schoenfeld residuals versus time

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Results

Parameter estimates

Table 1: Parameter estimates for the sub-distribution model for each event

Recurrence cGVHD Death

coef(se) exp(coef) coef(se) exp(coef) coef(se) exp(coef)
trt: PB -0.113 (0.9660) 0.893 0.319 (0.2079) 1.375 -1.573 (1.1069) 0.207
age -0.145 (0.0673)* 0.865 -0.012 (0.0092) 0.988 -0.092 (0.0506) 0.913
diag: CML -1.897 (1.2061) 0.150 0.540 (0.2284)* 1.715 -0.502 (0.8482) 0.606
Time-dependent variable
age 0.318 (0.1272)* 1.375 - - 1.221 (0.6077)* 3.389
∗
p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Results

Estimates of CIF

Figure 3: Model-based vs. non-parametric estimates of CIF

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Effect of Cell Harvesting Methods for Bone Marrow Transplantation on Multiple Events among Myeloid Leukemia Patients
Conclusion

Conclusion

▶ We found no significant difference between the effects of two stem

cell harvesting methods on time to each of three events (leukemia
recurrence, cGVH, and death), taking into account competing risk

▶ The results should be interpreted with limitation of small numbers of

events for leukemia recurrence and death (i.e., 5 events)

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