JCO Feb 2025

 Who gets TC?

1. ER positive, HER 2 neg stage I, stage II node neg

Taxol--AC

1. ER positive, stage II node positive, stage III

Triple neg stage I-- ok to do TC or AC-T

Triple neg higher stage - Key note 522 Neoadjuvant

HER 2 positive stage I- TH

HER 2 positive stage II or higher TCHP neoadjuvant

Blood journal snippets

 Blood journal Feb 2025

1.  Dual Asciminb and dasatinib inPh+ ALL and CML blast crisis:  80 mg asciminb+ dasatinib 140 mg daily  plus prednisone 60 mg/m2 for 28 days--> CHR84%. By day 84--> 100% complete hematologic response. After 28 day induction, the combination TKI was continued until transplant. Pancreatic enzyme elevation without pancreatitis was a toxicity. No vasoocclusion.

2. Blastic plasmacytoid dendritic neoplasm

- an aggressive heme malignancy derived from plasma dendritic cell

-IHC--> CD 123+, CD4 or CD56+, plus one other plasma cell dendritic cell marker CD303 or CD304. TET 2 mutations are common

- Mature dendritic cells lose CD56 which is not the case with BPDCN ( CD 56 positive)

-less than 0.5% incidence

-most common organ affected --> skin. CNS involvement can be 2 to 60%.

-CSF at baseline recommended for all patients with BPDCN regardless of CNS symptoms

-Ddx- AML with monocytic differentiation, CMML

-Rx--Induction with antiCD123 drug conjugate tagraxofusp ( Human IL-3 + truncated diphtheria toxin)

- Allo HCT in CR1; auto SCT can be considered in elderly IF no bone marrow involvement at presentation.

- even if pt has a localized skin presentation, XRT alone is futile and systemic chemo with allo HCT should be the goal

-front line options: none standard. Tagraxofusp or Venetoclax+ hyper CVAD, or ven+ Aza

From Open Evidence.

The treatment for blastic plasmacytoid dendritic cell neoplasm (BPDCN) has evolved significantly in recent years. The current first-line treatment for BPDCN is tagraxofusp, a CD123-targeted therapy. Tagraxofusp is a recombinant fusion protein that combines interleukin-3 with a truncated diphtheria toxin, and it has shown a high overall response rate in clinical trials. The typical dosage of tagraxofusp is 12 µg/kg administered intravenously on days 1 to 5 of a 21-day cycle.

For patients who achieve complete remission (CR) with tagraxofusp, allogeneic hematopoietic stem cell transplantation (allo-HCT) is recommended as a consolidative therapy, as it offers the best chance for long-term survival.[1][4] The National Comprehensive Cancer Network (NCCN) guidelines emphasize the importance of achieving CR before proceeding to allo-HCT.

In cases of relapsed or refractory BPDCN, treatment options include re-administration of tagraxofusp (if not previously used), chemotherapy, local radiation to isolated lesions, systemic steroids, and venetoclax-based regimens. Participation in clinical trials is also highly encouraged for these patients.

Close monitoring for adverse effects, particularly capillary leak syndrome, is crucial during tagraxofusp therapy.

Smoldering myeloma

 High risk smoldering

20/2/20

• BM clonal plasma cells 20% or higher
• M spike 2 gm or higher
• FLC involved to uninvolved 20 or higher.

Any 2 of the above: high risk SMM

The 2-year progression rate for high-risk patients is 46%.

Aquila trial- 

Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% 

Heparin induced thrombocytopenia

 Mortality- untreated HIT 20%

Autoantibody against heparin plus PF4 receptor on platelets ( similar to ternary mechanism in drug induced hemolytic anemia). Clinically significant type of HIT is type II.  Type I is a transient drop of plt within 2 days of heparin exposure. Type I is not clinically significant.

4T score calculator

1. If low probability--ct heparin, look for other causes. If OD 0.6 or less, this rules out HIT.

2. 4T score 4-5--> intermediate probability--> stop heparin. start non heparin anticoagulant. Send PF4 antibodies and SRA. If OD ≥2.00, consider the diagnosis of HIT to be confirmed per uptodate authors. If PF4 OD is between 0.6 and 1.99, send functional assay.

3. If a functional assay is not readily available, we use an OD >1.00 as confirmation of HIT in patients with an intermediate or high 4Ts score.

4.  4T 6-8 and an OD ≥1.50,  HIT confirmed; if the OD is between 0.60 and 1.49, we obtain a functional assay

Treatment

1. Discontinue heparin. Get US of all 4 extremities. If thrombosis documented, will need 3 months full dose anticoagulation, if no thrombosis, rx of heparin induced thrombocytopenia is treated for 30 days.

2. There are good data to support use of DOAC- Rivaroxaban, Apixaban, in the use of acute HIT without a preceding parenteral agent. For edoxaban and dabigatran, as was used in studies 5 days of parenteral anticoagulant is recommended in acute thrombosis.

3. Not much data to support argatroban in the treatment of acute HIT. Can use in pts going to surgery or who may need immediate reversal. Avoid argatroban in liver dysfunction. Argatroban may be preferred in kidney issues, although apixaban has been used.

4. Initiation of DOAC does not require platelet recovery. Transition when patient is clinically stable. No overlap. If pt is already on a parenteral agent such as argatroban or bivalirudin, start DOAC within 2 hours of stopping argatroban or bivalirudin infusion. DOAC start within 8-12 hours after stopping danaparoid infusion, and 24 hours after last dose of fondaparinux.

5. Pregnancy: fondaparinux The DOACs are contraindicated in individuals with a mechanical heart valve or during pregnancy or breastfeeding.

6. Role of IVIG: Individuals with platelet activation and thrombocytopenia from HIT-like antibodies in the absence of heparin exposure may need additional interventions to block platelet activation