BMT Flashcards
Rationale for HSCT -auto
Dose intensify chemotherapy
Stem cell rescue from myeloablative chemotherapy
Non-hematopoietic organ toxicity becomes dose-limiting
Rationale for HSCT -allo
Stem cell rescue from myeloablative chemotherapy
Establish a graft-versus- malignancy effect to destroy recipient cancer cells
Replace missing or abnormal hematopoietic component
Types of Transplant - anatomical source
Bone marrow (BMT)
Peripheral blood (PBSCT)
Umbilical cord blood (UCB
Types of Transplant - immunologic source
Allogeneic Matched related donor (MRD) Mismatched related donor (MMRD) or haploidentical Matched unrelated donor (MUD) Mismatched unrelated donor (MMUD)
Syngeneic
Autologous
Selection of HSC Source - Recipient Factors -4
Type and stage of recipient disease
Donor availability
Age
Performance status
Selection of HSC Source - Donor Factors -7
HLA match
Age
Sex
Number pregnancies in female donor
Blood type and ABO compatibility
Serologic status for cytomegalovirus
Matched race
HLA Matching -serology vs DNA
S: Identifies HLA molecules on the cell surface using antigen specific anti-sera
D: Identifies HLA molecules by defining the DNA code in the cell nucleus
slide 5C
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Umbilical Cord Blood Stem Cells - Advantages -5
Ease of procurement & faster availability than MUD
Lower immunogenicity in cord blood leading to lower rates of severe GVHD (permitting 1-2 antigen-mismatch)
Advantage of a lower transmission rate of infectious and genetic diseases
Increased units for ethnic minorities and patients with rare haplotypes
Frozen in small volumes; DMSO content is minimized
Umbilical Cord Blood Stem Cells - Disdvantages -5
Low number of stem cells in cord units
Cost
Lack of donor lymphocyte infusions
Lack of experience and long-term
outcomes
High rate of acquired infection
slide 6B
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most common source of marrow
kids: BM
adults: peri blood
Adult Acute Lymphoblastic Leukemia (ALL) Timing of Transplant Consultation -3
OS early tx 40%
what are high risk feautures -5
CR1 up to age 35 for standard risk
CR1 over age 35 if high risk
Poor-risk cytogenetics (e.g., (t(9;22 or 11q23))
High WBC (>30-50 x 109/L) at diagnosis
CNS or testicular leukemia
No CR within 4 weeks of initial treatment
Induction failure
CR2 and beyond
Adult ALL Key Recommendations -5
Allogeneic HSCT is recommended in CR1 for all risk groups based on a survival benefit &&&
Autologous HSCT is an alternative if there is no allogeneic donor (similar survival to maintenance chemo with shorter treatment duration)
Imatinib therapy before and after allogeneic HSCT should be considered
TBI based conditioning may be preferred
RIC only if they unsuitable for myeloablative
Adult Acute Myeloid Leukemia (AML) Timing of Transplant Consultation -3
OS early 50%
AML high risk feautures -3
High-risk AML including
Antecedent hematological disease (e.g., myelodysplastic syndromes)
Treatment-related leukemia
Induction failure
CR1 with poor-risk cytogenetics or molecular
markers
CR2 and beyond
Adult AML Key Recommendations -3
what about low risk cytogenetics? -1
intermediate risk? -1
Allogeneic HCST in CR1 confers a survival benefit over conventional chemotherapy in high-risk cytogenetics if patient < 55 years old
No survival advantage if low-risk cytogenetics
Unclear in intermediate risk cytogenetics
No advantage to autologous HSCT in CR1 over
conventional chemotherapy
Allogeneic HSCT in CR2 is recommended
Insufficient data to recommend a MUD over autologous HSCT
Myelodysplastic Syndrome (MDS) Timing of Transplant Consultation -3
OS early 40%
Intermediate-1 (INT-1), intermediate-2 (INT-2)
or high IPSS score which includes either:
> 5% marrow blasts
Other than good risk cytogenetics (good risk includes 5q- or normal)
> 1 lineage cytopenia
MDS Key Recommendations -2
Autologous is only recommended as part of a clinical trial
Allogeneic HSCT early in the disease course is recommended for
IPSS score of intermediate-2 or high risk
Have a suitable donor
Meet HSCT criteria
IPSS score of Intermediate -1 who have poor prognostic features not included in IPSS (older age, refractory cytopenias)
Chronic Myeloid Leukemia (CML)
Timing of Transplant Consultation -5
OS CP 70%
OS AP 40-45%
No hematologic or minor cytogenetic response 3 months post-imatinib initiation
No complete cytogenetic response 6-12 months post imatinib initiation
2nd Relapse
Accelerated phase
Blast crisis (myeloid or lymphoid)
CML Key Recommendations -1
&&&may be more- panotumib update
CML – Accelerated phase and blast crisis
Allogeneic HSCT as soon as CML – CP can be
achieved with TKI and/or chemotherapy
CLL Key Recommendations - 3
OS 40% (does not really flatten out)
def high risk CLL -3
Autologous HSCT
2 prospective RCT show improved EFS, but no
impact on overall survival (NOT DONE)
Allogeneic HSCT
Myeloablative conditioning generally not recommended because of high TRM (NOT DONE)
RIC considered for patients with high-risk CLL
1. Deletion 17p or 11q;
2. refractory to chemoimmunotherapy
3. who develop recurrence within 12 months after purine analog treatment
Non Hodgkin’s Lymphoma (NHL) Timing of Transplant Consultation - Diffuse large B-cell lymphoma -3
50% OS vs 30% with chemo insensitive dz (same as chemo)
At 1st or subsequent relapse
CR1 for patients with high or high-intermediate IPI risk
No CR with initial treatment
Non Hodgkin’s Lymphoma (NHL) Timing of Transplant Consultation - Follicular -4
Poor response to initial treatment
Initial remission duration < 12 months
Second relapse
Transformation to diffuse large B cell lymphoma
Non Hodgkin’s Lymphoma (NHL) Timing of Transplant Consultation - Mantle Cell Lymphoma -3
Following initial therapy
NHL Key Recommendations - DLBCL -2
Autologous HSCT recommended in 1st
chemosensitive relapse as it improves survival
Not recommended in 1st CR for any IPI risk or in partial remission after 3 cycles of chemotherapy
NHL Key Recommendations - FL -4
Autologous HSCT recommended for transformed follicular lymphoma
Autologous HSCT NOT recommended in CR1
No overall survival benefit
No comparative data with rituximab-containing regimens
Higher incidence of therapy related AML/MDS
NHL Key Recommendations - mantle cell -1
Many experts recommend autologous HSCT in CR1
PROBABLY NOT TESTABLE
Hodgkin’s Disease Timing of Transplant Consultation -2
OS CR 70%
OS not CR sens 60%
OS not CR insens 40%
No initial CR
1st or subsequent relapse
Hodgkin’s Disease Key Recommendations -3
Autologous HSCT is recommended in 1st chemosensitive relapse -outcomes improved over conventional therapy in randomized trials
Autologous HSCT is recommended in patients with refractory disease- outcomes improved over conventional therapy
RIC Allogeneic considered in eligible patients with no other options (including clinical trials)