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NCCN > B CELL LYMPHOMA > Flashcards

B CELL LYMPHOMA Flashcards

1
Q

Typical immunophenotype FL:

A

CD10+, BCL2+, CD23+/-, CD43-, CD5-, CD20+, BCL6+

Rare cases of FL may be CD10- or BCL2-.

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2
Q

Anti-CD20 mAbs for FL include:

A

Rituximab or obinutuzumab

Obinutuzumab is not indicated as single-agent therapy.

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3
Q

Consider possibility of histologic transformation in patients with:

A
  • Progressive disease, especially if LDH levels are rising
  • Single site is growing disproportionately
  • Extranodal disease develops
  • There are new B symptoms
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4
Q

Preferred treatment for: Stage I or Contiguous stage II FL

A

ISRT

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5
Q

Type of FL

Morphology: expansile follicles, effacement of architecture, absence of diffuse area

Presents as localized disease (stage I, II)

Male sex predominant

Younger age than typical FL (though can occur in adults >60 years)

A

Pediatric type Follicular Lymphoma

If the patient has disease >stage II, it is by definition not PTFL.

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6
Q

Immunophenotype of Pediatric FL:

A

Expresses: BCL6, CD10, ± IRF4/ MUM1 (~20%)

Proliferation index (Ki-67/MIB-1) >30%

No rearrangement of BCL2, BCL6, IRF4/MUM1

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7
Q

Preferred treatment for Pediatric FL:

A

Excision

RCHOP for patients with extensive local disease who are not candidates for excision or ISRT

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8
Q

Guide for initiation of treatment in FL

GELF CRITERIA

A
  • Involvement of ≥3 nodal sites, each with a diameter of ≥3 cm
  • Any nodal or extranodal tumor mass with a diameter of ≥7 cm
  • B symptoms
  • Splenomegaly
  • Pleural effusions or peritoneal ascites
  • Cytopenias (leukocytes <1.0 x 109/L and/or platelets <100 x 109/L)
  • Leukemia (>5.0 x 109/L malignant cells)
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9
Q

Prognostic Index for FL

FLIPI - 1 CRITERIA

A
  • Age ≥60 y
  • Ann Arbor Stage III-IV
  • Hemoglobin level <12 g/dL
  • Serum LDH level >ULN (upper limit of normal)
  • Number of nodal sites ≥5

Low 0-1
Intermediate 2
High ≥3

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10
Q

Preferred regimens high tumor burden FL

A
  • Bendamustine + obinutuzumab or rituximab
  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
    + obinutuzumab or rituximab
  • CVP (cyclophosphamide, vincristine, prednisone) + obinutuzumabe or rituximab
  • Lenalidomide + rituximab
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11
Q

Preferred regimens low tumor burden FL

A

Rituximab (375 mg/m2 weekly for 4 doses)

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12
Q

Preferred regimens older patients with FL

A

Rituximab (375 mg/m2 weekly for 4 doses)

Other recommended regimens
* Chlorambucil ± rituximab
* Cyclophosphamide ± rituximab

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13
Q

Preferred regimens extended therapy or maintainance

A
  • Rituximab maintenance 375 mg/m2 one dose every 8–12 weeks for 2 years for patients initially presenting with high tumor burden (category 1)
  • Obinutuzumab maintenance (1 g every 8 weeks for 12 doses)

If initially treated with single-agent rituximab, rituximab maintenance 375 mg/m2 one dose every 8 weeks for 4 doses

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14
Q

Preferred regimens third line and subsequent therapy

A

T-cell engager therapy
Bispecific antibody therapy
- Epcoritamab-bysp
- Mosunetuzumab-axgb

Chimeric antigen receptor (CAR) T-cell therapy
- Axicabtagene ciloleucel (CD19-directed)
- Lisocabtagene maraleucel (CD19-directed)
- Tisagenlecleucel (CD19-directed)

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15
Q

A EZH2 inhibitor for FL

A

Tazemetostat

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16
Q

BTK inhibitor (BTKi) for FL

A

Zanubrutinib

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17
Q

TRUE OR FALSE

Diagnosis of EMZL of the stomach requires an endoscopic biopsy.

A

TRUE

Diagnosis of EMZL of the stomach requires an endoscopic biopsy.

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18
Q

Typical immunophenotype of Extranodal Marginal Zone B-Cell Lymphoma/Gastric :

A

CD10-, CD5-, CD20+, cyclin D1-, BCL2- follicles

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19
Q

Treatment for Stage I/III EMZL

H.pylori positive, t(11;18) negative, or t(11;18) unknown

A

Antibiotic therapy for H. pylori

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20
Q

Treatment for Stage I/III EMZL

H.pylori positive, t(11;18) positive

A

Antibiotic therapy for H. pylori + ISRT

Antibiotic therapy for H. pylori + Rituximab (if ISRT is contraindicated)

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21
Q

Treatment for Stage I/III EMZL

H. pylori negative

A

ISRT

Rituximab (if ISRT is contraindicated)

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22
Q

Preferred treatment for Stage III/IV EMZL

A
  • Bendamustine + rituximab
  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab
  • CVP (cyclophosphamide, vincristine, prednisone) + rituximab

Other recommended regimens
* Lenalidomide + rituximab (category 2B)
* Rituximab (375 mg/m2 weekly for 4 doses) for EMZL and nodal MZL

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23
Q

Karyotype that has locally advanced disease and is a predictor for lack of tumor response (<5%) to antibiotics

A

t(11;18)

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24
Q

Molecular analysis that help differentiate Waldenström macroglobulinemia (WM) (90%) versus MZL (10%) if plasmacytic differentiation present

A

MYD88 mutation status

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25
Q

Indications for treatment in EMZL

A
  • Symptoms
  • Gastrointestinal (GI) bleeding
  • Threatened end-organ function
  • Clinically significant bulky disease
  • Steady or rapid progression

Surgical resection is generally limited to specific clinical situations (ie, life-threatening hemorrhage).

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26
Q

Restaging with endoscopy/biopsy for H. pylori/lymphoma after antibiotics is done after

A

6 months

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27
Q

Restaging with endoscopy/biopsy for H. pylori/lymphoma after ISRT or rituximab is done after

A

6 months

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28
Q

Typical nongastric sites of EMZL include the following:

A

Bowel (small and large), breast, head and neck, lung, dural, ocular adnexa, ovary, parotid, prostate, and salivary gland

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29
Q

Based on anecdotal responses to antibiotics in ocular and cutaneous marginal zone lymphomas, some physicians will give an empiric course of ____________ prior to initiating other therapy.

A

Doxycycline

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30
Q

TRUE OR FALSE

MZL is rare and occurs most commonly as spread from extranodal sites

A

TRUE
‘
MZL is rare and occurs most commonly as spread from extranodal sites

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31
Q

SMZL is most definitively diagnosed at _________________

A

Splenectomy

Since the immunophenotype is nonspecific and morphologic features on the bone marrow may not be diagnostic

However, the diagnosis of SMZL may be made on the basis of bone marrow ± peripheral blood involvement by small lymphoid cells with Ig light chain restriction that lack characteristic features of other small B-cell neoplasms (ie, CD5, CD10, cyclin D1)

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32
Q

Typical immunophenotype of SMZL:

A

CD10-, CD5-, CD20+, CD23-/+, CD43-/+, and cyclin D1-, BCL2- follicles, annexin A1, and CD103- (distinction from hairy cell leukemia [HCL]) with expression of both IgM and IgD

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33
Q

May be helpful to differentiate SMZL from other B-cell lymphoma subtypes.

A

NOTCH2 and KLF2 mutation

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34
Q

Prefrred treatment for SMZL with splenomegaly, HCV negative, with symptoms and cytopenias

A

Rituximab

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35
Q

Typical immunophenotype of MCL:

A

CD5+, CD20+, CD43+, CD23-/+, cyclin D1+, CD10-/+.

Note: Some cases of MCL may be CD5- or CD23+.

If the diagnosis is suspected, cyclin D1 staining or FISH for t(11;14) should be done.

There are rare cases of CCND1- MCL (< 5%) with an otherwise typical immunophenotype.

36
Q

Most common biomarker for indolent disease:

A

SOX11- [IGHV mutated]

37
Q

Features of indolent MCL:

A
  • Leukemic non-nodal CLL-like with splenomegaly
  • GI or blood/ bone marrow involvement only
  • Low tumor burden
  • Ki-67 proliferation fraction <10%
38
Q

Preferred Aggressive induction therapy for MCL:

A
  • LyMA regimen: RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) x 4 cycles followed by RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for non-PET CR
  • NORDIC regimen: Dose-intensified induction immunochemotherapy with rituximab + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP) alternating with rituximab + high-dose cytarabine
  • Rituximab, bendamustine followed by rituximab, high-dose cytarabine
  • TRIANGLE regimen: Alternating RCHOP + covalent BTKi/RDHA (rituximab, dexamethasone, cytarabine) + platinum
    (carboplatin, cisplatin, or oxaliplatin) (category 2A for ibrutinib; category 2B for acalabrutinibj or zanubrutinib)

Other recommended regimen
* HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) + rituximab
* RBAC500 (rituximab, bendamustine,c cytarabine)

39
Q

Preferred Less aggressive induction therapy for MCL

A
  • Bendamustine + rituximab
  • VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone)
  • RCHOP
  • Lenalidomide (continuous) + rituximab
40
Q

Induction Therapy

(STAGE II BULKY OR NONCONTIGUOUS, III, OR IV MCL; CLASSICAL TP53 MUTATED)

A

Zanubrutinib/obinutuzumab/venetoclax

41
Q

MAINTENANCE AFTER HDT/ASCR OR AGGRESSIVE INDUCTION THERAPY

A

Covalent BTKi x 2 yearsh (category 2A for ibrutinib; category 2B for acalabrutinib or zanubrutinib) + rituximab every 8 weeks x 3 years

42
Q

MAINTENANCE AFTER LESS AGGRESSIVE INDUCTION THERAPY

A
  • Rituximab every 8 weeks for 2–3 years following RCHOP (category 1) or
  • Bendamustine + rituximab
43
Q

Typical immunophenotype DLBCL:

A

CD20+, CD45+, CD3-

44
Q

Definition of bulky in DLBCL

A

≥7.5 cm

Some studies have used 10 cm as the cutoff for bulky disease.

45
Q

TRUE OR FALSE

In testicular lymphoma, after completion of chemoimmunotherapy, scrotal RT should be given.

A

TRUE

In testicular lymphoma, after completion of chemoimmunotherapy, scrotal RT should be given.

46
Q

The optimum timing of end-of-treatment PET/CT is unknown; however, waiting a minimum of ______________ weeks after RT to repeat PET/CT scan is suggested.

A

8 weeks

47
Q

INTERNATIONAL PROGNOSTIC INDEX

A
  • Age >60 years
  • Serum LDH > normal
  • Performance status 2–4
  • Stage III or IV
  • Extranodal involvement >1 site

  • Low 0 or 1
  • Low-intermediate 2
  • High-intermediate 3
  • High 4 or 5
48
Q

AGE-ADJUSTED INTERNATIONAL PROGNOSTIC INDEX ≤60 YEARS

A
  • Serum LDH > normall
  • Stage III or IV
  • Extranodal involvement >1 site

  • Low 0
  • Low-intermediate 1
  • High-intermediate 2
  • High 3
49
Q

STAGE-MODIFIED INTERNATIONAL PROGNOSTIC INDEX (smIPI)

A
  • Age >60 years
  • Serum LDH > normal
  • Performance status 2–4
  • Stage II or IIE

  • Low 0 or 1
  • High 2–4
50
Q

NCCN-IPI

A

Age, years
* >40 to ≤60 1
* >60 to <75 2
* ≥75 3
LDH, normalized
* >1 to ≤3 1
* >3 2
Ann Arbor stage III–IV 1
Extranodal disease 1
Performance status ≥2 1

Extranodal: Disease in bone marrow, CNS, liver/GI tract, or lung.

51
Q

PROGNOSTIC MODEL TO ASSESS THE RISK OF CNS DISEASE
CNS IPI

A
  • Age >60 years
  • Serum LDH > normal
  • Performance status >1
  • Stage III or IV
  • Extranodal involvement >1 site
    * Kidney or adrenal gland involvement

  • Low risk 0–1
  • Intermediate-risk 2–3
  • High-risk 4–6 or kidney or adrenal gland involvement
52
Q

Additional indications for CNS prophylaxis independent of CNS risk score

A
  • Testicular lymphoma
  • Primary cutaneous DLBCL, leg type
  • Stage IE DLBCL of the breast
  • Kidney or adrenal gland involvement
53
Q

If CNS prophylaxis is used, options include:

A
  • Systemic high-dose methotrexate (3–3.5 g/m2 for 2–4 cycles) during or after the course of treatment and/or
  • IT methotrexate and/or cytarabine (4–8 doses) during or after the course of treatment
54
Q

A mature aggressive B-cell lymphoma characterized by large cells with plasmablastic differentiation and cytoplasmic expression of ALK, and lacking CD20 expression

A

ALK-positive DLBCL

EBV and HHV8 are negative in ALK-positive LBCL, and there is no association with immune deficiency.

t(2;17)(p23;q23), denoting the CLTC (clathrin heavy chain)/ ALK fusion

The median age at diagnosis is approximately 40 years and there is a strong male predominance.

Most patients present with rapidly progressive disease at advanced stage, and both nodal and extranodal involvement are common.

55
Q
  • Present with large anterior mediastinal mass with or without supraclavicular lymph nodes.
  • More common in males, presenting between 20–40 y
  • Typically larger and more pleomorphic than in PMBL, sometimes resembling lacunar or Hodgkin-like cells.
  • A worse prognosis than either CHL or PMBL has been suggested.
A

MEDIASTINAL GRAY ZONE LYMPHOMA (MGZL)

56
Q

Typical immunophenotype of MGZL:

A

CD45+, PAX5+, BOB.1+, OCT-2+, CD15+, CD20+, CD30+, and CD79a+; CD10- and ALK-

BCL6 is variably expressed and EBV is usually negative

57
Q

Preferred for DLBCL
* Stage I–II
* Stage II (with extensive mesenteric disease) or Stage III–IV

A
  • RCHOP
  • Pola-R-CHP
58
Q

Regimens for DLBCL Patients with Poor Left Ventricular Function

A
  • DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) + rituximab
  • RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone)
  • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone)
  • RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine,
    prednisone)
  • RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, procarbazine) (category 2B)
59
Q

Regimens for DLBCL Very Frail Patients and Patients >80 Years of Age with Comorbidities

A
  • RCDOP
  • R-mini-CHOP
  • RGCVP
  • RCEPP (category 2B)
60
Q

Regimen for concurrent presentation with CNS Disease

A
  • Parenchymal: systemic high-dose methotrexate (≥3 g/m2 given with RCHOP cycle that has been supported by growth factors).
  • Leptomeningeal: IT methotrexate/cytarabine, consider Ommaya reservoir placement. OR
    Systemic high-dose methotrexate (3–3.5 g/m2) can be given in combination with RCHOP or as consolidation after RCHOP + IT methotrexate/cytarabine

Different schedules have been used for the integration of high-dose methotrexate with RCHOP (early- or mid-cycle or day 15 of a 21-day cycle)

61
Q

Preferred therapy for DLBCL Secondline therapy (intention to proceed to transplant):

A
  • DHA (dexamethasone, cytarabine) + platinum (carboplatin,
    cisplatin, or oxaliplatin) ± rituximab
  • GDP (gemcitabine, dexamethasone, cisplatin) ± rituximab or (gemcitabine, dexamethasone, carboplatin) ± rituximab
  • ICE (ifosfamide, carboplatin, etoposide) ± rituximab
62
Q

Preferred therapy for DLBCL Secondline therapy (no intention to proceed to transplant):

A
  • CAR T-cell therapy (CD19-directed)k (if eligible)
    Lisocabtagene maraleucel
  • Polatuzumab vedotin-piiq ± bendamustinel ± rituximab
  • Tafasitamab-cxixl + lenalidomide
63
Q

Preferred therapy for DLBCL Secondline therapy (relapsed disease <12 mo or primary refractory disease):

A

CAR T-cell therapy
* Axicabtagene ciloleucel (CD19-directed) (category 1)
* Lisocabtagene maraleucel (CD19-directed) (category 1)

64
Q

Can be defined as a clinical entity presenting with primary site of disease in the anterior mediastinum with or without other sites and has histology of DLBCL

A

Primary Mediastinal Large B-Cell Lymphoma

65
Q

First line therapy for Primary Mediastinal Large B-Cell Lymphoma

A
  • Dose-adjusted EPOCH-rituximab
  • RCHOP-21 x 6 cycles
  • RCHOP-14 followed by ICE
66
Q

Therapy for R/R Primary Mediastinal Large B-Cell Lymphoma

A
  • Pembrolizumab
  • Nivolumab ± brentuximab vedotin
  • Manage as relapsed/refractory DLBCL
67
Q

LBCL with MYC and BCL2 or BCL6 rearrangements as detected by FISH or standard cytogenetics are known as.

A

“double-hit” lymphomas

If all three rearrangements present, they are referred to as “triple-hit” lymphomas.

The vast majority are germinal center B-cell (GCB)–like lymphomas.

Patients often present with poor prognostic variables, such as elevated LDH, bone marrow and CNS involvement, and a high IPI score.

68
Q

Typical immunophenotype of BL:

A

sIg+, CD10+, CD20+, TdT-, Ki-67+ (≥95%), BCL2-, BCL6+

69
Q

Most common karyotype is _______ rearrangement as a sole abnormality.

A

MYC rearrangement

70
Q

There is an uncommon variant of BL without MYC rearrangement but with 11q aberration

A

LBCL with 11q aberration [ICC]
HGBL with 11q aberrations [WHO5]

Optimum management of this rare subtype is undefined, though it is most often treated like typical BL.

71
Q

Low Risk BL

A
  • Normal LDH
  • Stage I and Completely resected abdominal lesion
  • Single extraabdominal mass <10 cm
72
Q

High Risk BL

A
  • Stage I and Abdominal mass
  • Single extraabdominal mass >10 cm
  • Stage II–IV
73
Q

TRUE OF FALSE

CHOP is an adequate therapy for BL.

A

FALSE

CHOP is an adequate therapy for BL.

74
Q

Preferred regimens for BL

A
  • CODOX-M (original or modified) (cyclophosphamide, doxorubicin, vincristine with intrathecal [IT] methotrexate and cytarabine followed by high-dose systemic methotrexate) + rituximab
  • Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) + rituximab
  • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) alternating with high-dose methotrexate
    and cytarabine + rituximab (regimen includes IT therapy)

For High Risk: Started with the portion of the systemic therapy that contains CNS-penetrating drugs:
* CODOX-M alternating with IVAC
* HyperCVAD
* Dose-adjusted EPOCH intrathecal methotrexate- for patients with high-risk BL and with baseline CNS disease not able to tolerate aggressive treatments

Prophylaxis for tumor lysis syndrome is mandatory

75
Q

Preferred regimen for BL ≥60 y Low and High Risk

A

Dose-adjusted EPOCH

76
Q

HIV-Related B-Cell Lymphomas

In general, avoidance of the ff ARV __________________ is strongly recommended.

A

Zidovudine, cobicistat, and ritonavir

Antiretroviral therapy (ART) can be administered safely with chemotherapy

77
Q

Preferred Regimens for HIV-BL

A
  • Modified CODOX-M/IVAC/rituximab
  • Dose-adjusted EPOCH/rituximab

  • If CD4 < 50, maximize supportive care and monitor closely for cytopenias and infections while administering lymphoma therapy
  • Granulocyte colony-stimulating factor (G-CSF) for all patients
78
Q

Preferred regimens for HIV-DLBCL, HHV8 POSITIVE DLBCL, NOS, PEL

A
  • EPOCH/rituximab

  • RCHOP
79
Q

Initial treatment for HIV-DLBCL R/R

A
  • Bortezomib/ICE
  • Bortezomib/ICE/rituximab
80
Q

Preferred regimens for HIV-Plasmablastic Lymphoma

A
  • EPOCH

  • Modified CODOX-M/IVAC
  • HyperCVAD
81
Q

RECOMMENDATIONS FOR EPOCH ± RITUXIMAB DOSE ADJUSTMENTS FOR NON-BURKITT LYMPHOMAS

A

Day 5 cyclophosphamide dosing
* If baseline CD4 count is > 200cells/mm3, start cyclophosphamide at 750 mg/m2
* If baseline CD4 count is 50–200 cells/mm3, start cyclophosphamide at 375 mg/m2
* For baseline CD4 counts < 50 cells/mm3, cycle 1 doses of cyclophosphamide above 187.5 mg/m2 have not been published

  • Rituximab (if CD20-positive) 375 mg/m2 IV on Day 1
  • Etoposide 50 mg/m2/day continuous IV infusion for 4 days (96 hours)
  • Doxorubicin 10 mg/m2/day continuous IV infusion for 4 days (96 hours)
  • Vincristine 0.4 mg/m2/day continuous IV infusion for 4 days (96 hours)
  • Prednisone 60 mg/m2/day for 5 days
82
Q

Typical immunophenotype: B-LL:

A

sIg-, CD10+/-, CD19+, CD20-/+, TdT+, CD34+, CD79a+

83
Q

Typical immunophenotype T-LL:

A

sIg-, CD10-, CD19/20-, CD3-/+, CD4/8+/+, CD1a+/-, TdT+, CD2+, CD7+ cytoplasmic CD3+, sCD3-/+

84
Q

B Cell Neoplasm: Small cells

A
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
  • Mantle cell lymphoma (MCL)
  • Splenic marginal zone lymphoma (SMZL)
  • Hairy cell leukemia (HCL)
  • Lymphoplasmacytic lymphoma (LPL)
  • Extranodal marginal zone lymphoma (EMZL)
  • Nodal marginal zone lymphoma (NMZL)
  • Follicular lymphoma (FL)
  • Pediatric-type follicular lymphoma (PTFL)
85
Q

B Cell Neoplasm: Medium cells

A
  • Burkitt lymphoma (BL)
  • MCL, blastoid variant
  • High-grade B-cell lymphoma (HGBL), NOS
  • HGBL with MYC and BCL2 rearrangements (ICC and WHO-5
  • HGBL with MYC and BCL6 rearrangements (ICC)
  • LBCL with 11q aberration [ICC]; HGBL with 11q aberrations [WHO]
86
Q

B Cell Neoplasm: Large cells:

A
  • Diffuse large B-cell lymphoma (DLBCL), NOS
  • DLBCL associated with chronic inflammation
  • Lymphomatoid granulomatosis
  • Primary mediastinal large B-cell lymphoma (PMBL)
  • Intravascular LBCL
  • ALK-positive LBCL
  • Plasmablastic lymphoma
  • HHV8+ LBCL, NOS
  • LBCL with IRF4 rearrangement
  • Primary effusion lymphoma (PEL)
  • Mediastinal gray zone lymphoma (MGZL)
  • MCL, pleomorphic variant
87
Q

Viral condition that can arise from use of anti-CD20 mAb Therapy and Brentuximab Vedotin

A

Progressive multifocal leukoencephalopathy (PML):

NCCN (13 decks)

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