ALL

ALL

ALL Part 1

What defines consolidation therapy for Philadelphia chromosome positive ALL?

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Allogenic stem cell transplant or TKI+chemo regimen

ALL Part 1
ALL

What is the role of autologous stem cell transplant for relapsed or refractory ALL?

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No role

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Is there are difference in leukemia-free survival in the high- and low-risk relapsed or refractory ALL population status post allogenic stem cell transplant in CR2?

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Yes, low risk is 45% survival while high risk is 15% survival

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Is there are difference in leukemia-free survival in the high- and low-risk relapsed or refractory ALL population status post allogenic stem cell transplant in CR2?

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Yes, low risk is 45% survival while high risk is 15% survival

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What is the 3-year leukemia free survival for relapsed and refractory ALL with allogeneic stem cell
transplant without CAR-T ?

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12-25%

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What is the incidence of central nervous system disease at first diagnosis and first relapse for ALL?

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First diagnoses 5%, relapse 20-30%

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What defines a CR for ALL after induction?

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<5% blasts>25% BM cellularity

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Is there randomized data supporting maintenance chemotherapy following allogeneic stem cell
transplant for ALL?

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No

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How should you manage high risk patients with ALL?

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Induction chemotherapy and then evaluation for allogeneic stem cell transplant after CR1

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What are some variables that predict for decreased allogenic stem cell survival?

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Philadelphia chromosome positive disease, undifferentiated phenotype, common ALL (CD10+), age older
than 35, white blood cell count greater than 30,000, CR1 after day 28

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How many risk stratifications are there for ALL?

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Standard risk and high risk
High risk should be evaluated for allogeneic stem cell transplant

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How do autologous stem cell transplant and maintenance chemotherapy compare in ALL?

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Equivalent

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Which chemotherapy drugs comprise the maintenance portion for ALL treatment ?

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6-MP, steroids, vincristine, methotrexate

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What are good risk FISH/Cytogenetic changes?

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Deletion 9p, 14q11-13, high hyperdiploidy

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Which FISH / Cytogenetic study findings correlate to poor risk ALL?

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t(9;22) t(1;19) t(4;11) t(8;14)

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What are the poor-risk features of ALL?

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Complex karyotype, Philadelphia chromosome positive, CR1 greater than 28 days, pre-B phenotype,
MRD+, Age >60, Hyperdiploidy WBC >30k (B-cell) and >100k (T-cell)

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What are the good-risk features of ALL?

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Age less than 30, mediastinal mass, white blood cell count less than 30,000, no Philadelphia
chromosome

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What are 3 treatment options for consolidation in ALL?

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Chemotherapy, autologous stem cell transplant, allogeneic stem cell transplant

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How can you manage ALL with + CNS involvement?

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Whole brain radiation with 2400 cGy and at least 6 intrathecal methotrexate injections

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What induction option is there for frail/elderly patients with Philadelphia chromosome positive ALL?

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TKI + steroids

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When can you use Ponatinib in Ph+ ALL?

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T315I mutation only

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What is the primary advantage of using dasatinib in Philadelphia chromosome positive ALL?

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Passes the blood-brain barrier

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What is the median overall survival for Philadelphia chromosome positive ALL with only induction
chemotherapy?

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6-9 months

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Which TKI has the least data in Philadelphia chromosome positive ALL?

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Bosutinib

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What is a low intensity regimens for ALL that can be used in unfit/geriatric patients?

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Vincristine plus steroids

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How can you distinguish chronic myeloid leukemia blast crisis transformation from Philadelphia
chromosome positive ALL?

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Unable to distinguish

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ALL

What is the mortality with induction difference between patients less than 60 and older than 60 for
HyperCVAD ?

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2% versus 15%

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What are the 5 phases of the CALGB 10403 protocol?

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Induction, consolidation, primary maintenance, delayed intensification, secondary maintenance

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How can you monitor the efficacy of L-asparaginase during ALL treatment?

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Check drug level at day 7 and 14 to determine if there is silent inactivation

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In patients with LBL with a very high risk of tumor lysis syndrome, what first-line treatment can be
started?

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Prednisone plus cyclophosphamide

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What defines a complete response in bone marrow biopsy for ALL therapy?

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<5% blasts>/= 25% cellularity

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What is a unique chemotherapy side effect with Down syndrome during ALL treatment?

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High sensitivity to methotrexate

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What treatment regimen is used for adult T-cell ALL/LBL?

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Same regimen as B-cell ALL

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What demographic and what presentation is common for T-cell ALL/LBL?

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Young male with a mediastinal mass

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What blast percentage distinguishes lymphoblastic lymphoma versus ALL?

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25%

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Which lymphoma is on a diagnostic continuum with ALL?

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Lymphoblastic lymphoma

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Which surface marker is almost always positive in ALL?

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TdT

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Which IHC stain is positive in AML and negative in ALL?

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MPO

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Which surface antigen is only seen in the late pre-B-cell ALL?

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CD20

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What prognostic value is there in Ig gene and TCR gene rearrangement studies in ALL?

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None

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What defines hyper- and hypodiploidy in ALL?

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Hyper 51-65 chromosomes = good prognosis
Hypo <45 chromosomes poor prognosis

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Which translocation is most common in adult ALL?

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t(9;22) seen in 25% of adults, 50% of those are in adults older than 60

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Which important transcription factor is lost in Philadelphia chromosome positive ALL?

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Ikaros

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What IHC pattern for ALL distinguishes B-cell from T-cell origin?

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CD3- CD19/20/79a/22+ = B-cell origin

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How can you quickly distinguish ALL versus AML by IHC?

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TdT+ MPO- = ALL

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Which pediatric ALL genetic rearrangement confirms a poor prognosis in adults?

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MLL

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Which chromosome translocation confirms a good prognosis in ALL?

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t(12;21) ETV6:RUNX1

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Which ALL regimens have been prospectively compared?

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None

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Which 4 regimens are commonly used ALL treatment?

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CALGB , BFM, HyperCVAD, GRAALL-2003

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Which ALL patients with CD20 positive disease would benefit from rituximab?

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Younger than 60 years old

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Which enzyme should be tested prior to treating with 6-MP?

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TPMT

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Which 3 cytotoxic agents form the backbone of the majority of AML regimens?

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Prednisone, vincristine, anthracycline

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ALL

What is the approximate complete response rate for ALL induction regimens such as BFM and
HyperCVAD?

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80%, high relapse rate without consolidation maintenance

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Which ALL regimen does not contain L-asparaginase?

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Hyper-CVAD

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What are the most active cytotoxic agents in ALL treatment?

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Anthracycline, alkylating agents, steroids, vinca alkaloids, folate inhibition, DNA polymerase inhibiters

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What are the5 main complications of L-asparaginase?

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Thrombosis, pancreatitis, allergic reaction, triglyceride and liver enzyme elevation

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Which asparaginase formulations are available in the United States?

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Erwinia derived and PEG-asparginase

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What is the most concerning side effect with hyper-CVAD which limits use in elderly patients?

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Prolonged myelosuppression

ALL
ALL Part 2

Which of the induction ALL regimens have been compared head to head ?

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None

ALL Part 2
ALL

Is there phase 3 data supporting the use of rituximab with HyperCVAD in B-cell ALL ?

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No, only phase 2

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Was there an improvement in 2-year EFS with the addition of rituximab to induction chemo with B-cell ALL ?

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Yes

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What did the GRAALL-2005/R trial assess ?

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Rituximab added to standard induction chemo in CD20 positive B-cell ALL

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What did the EORTC 58881 trial determine about IV 6-MP versus oral 6-MP ?

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It is detrimental to change oral 6-MP to IV 6-MP as part of maintenance

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Is there phase 1,2 or 3 data supporting the use of clofarabine in r/r B-cell ALL ?

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Phase 2 only

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Was an OS shown in the INO-VATE-ALL trial ?

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Yes

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What did the INO-VATE-ALL trial assess ?

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Inotuzumab ozogamicin in r/r B-cell ALL versus cytarabine, FLAG, and Mitoxantrone/Cytarabine

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What did the ELIANA trial assess ?

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Tisagenlecleucel in r/r B-cell ALL

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What did the TOWER trial assess ?

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Blinatumomab in r/r B-cell ALL

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Which trial assessed the utility of ponatinib in the r/r Ph+ B-cell ALL setting ?

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PACE

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Is any particular TKI used in r/r Ph+ B-cell ALL supported by phase 3 data ?

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No, all phase 2

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Is the use of bliontumomab in the r/r setting for Ph+ B-cell ALL supported by phase 3 data ?

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No , only phase 2

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Was an EFS shown in the POG 9404 trial ?

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Yes, both 5-year and 10-year

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What did the POG 9404 trial assess ?

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The efficacy of high-dose MTX added to Doxorubicin Asparaginase, Mercaptopurine, Vincristine,
Prednisone

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What comprised the consolidation phase of COG AALL0434 trial in T-cell ALL ?

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Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine

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What comprised the induction phase of COG AALL0434 trial in T-cell ALL ?

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DOLP – Daunorubicin, Pegaspargase, Vincristine, Prednisone induction

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What was the purpose of the COG AALL0434 trial in T-cell ALL ?

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To determine the efficiacy of integrating nelarabine with intensive chemo (in the consolidation phase)

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What are the 2 dosing regimens for nelarabine in T-cell ALL ?

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650mg/m2 Days 1-5 or 1250mg/m2 Days 1,3,5

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Does reduction of GVHD prophylaxis improve survival and improve GVL effect in Ph+ ALL patients with MRD?

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No, less intensive GVHD prophylaxis has not been shown to improve GVL effect

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Is there a higher mortality associated with transplant associated TMA ?

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Yes

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Which malignancies have the highest associated risk for transplant associated -TMA ?

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ALL and severe aplastic anemia

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Is there data to support the use of liposomal vincristine in the HyperCVAD regimen for B-cell ALL?

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Yes, Hyper-CMAD regimen

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Is later relapse (> 3 years from CR1) a better or worse prognostic marker in adult B-cell ALL patients that undergo transplant ?

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Better

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What is the active metabolite of 6-MP ?

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6-thioguanine nucleotide

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What is the active metabolite of 6-MP ?

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6-thioguanine nucleotide

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Is adult B-cell ALL with hyperdiploidy a favorable or poor prognostics group ?

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Good

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What defines hypodiploidy ?

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< 44 chromosomes

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What percent of adult ALL is Ph chromosome positive ?

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25%

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What is the median age of ALL diagnosis ?

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15

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What percent of ALL diagnoses are in those older than 65 ?

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Less than 15%

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Can tisagenlecleucel be used for Ph+ r/r B-cell ALL ?

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Yes , can be used for both Ph+ and Ph –

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Which portion of the BCR-ABL fusion protein should be sequenced for TKI refractory cases ?

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ABL1 kinase domain

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What are some treatment options besides transplant for r/r B-cell ALL ?

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Bliatumomab, tisagenlecleucel, and inotuzumab ozogamicin

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What comprises the maintenance chemo for B-cell ALL ?

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6-MP, MTX, vincristine, prednisone

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How can you manage a patient with Ph- B-ALL that has a complete remission after induction chemo but has detectable MRD ?

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Bliatumomab followed by allo-HSCT

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What is the minimum duration of TKI post-Allo-HSCT in PH+ B-ALL ?

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1 year

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When would you consider TKI + steroids alone for a young patient with Ph+ B- ALL ?

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Induction only, further chemo should be planned

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What is the incidence of secondary ALL?

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2-10%

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How would you treat “Philadelphia chromosome like” ALL with ETV6-NTRK3 fusion protein?

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Crizotinib

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Which Philadelphia chromosome positive ALL patients do not benefit from a transplant?

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Younger than 21 years old

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How would you treat a “Philadelphia chromosome like” ALL with EPOR fusion protein?

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Ruxolitinib

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What is the minimum time between induction and relapse in ALL where re-challenge with the same
regimen can be attempted?

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2 years

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What is the ideal CMV donor recipient status in ALL transplant?

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Donor positive recipient negative

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Which translocation produces the MLL gene rearrangement in ALL?

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t(v;11q23)

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What is the role of TKI following allogeneic stem cell transplant for Ph+ ALL?

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Unclear, but 2 years of therapy is generally recommended

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Are there randomized trials comparing allogeneic stem cell transplant for consolidation chemotherapy
plus TKI versus observation in Ph+ ALL?

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No
2-year overall survival is roughly 60%

ALL
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