"adult T-cell leukemia lymphoma" HTLV-1 diagnosis treatment

PMID: 37300656

mkdir -p /home/daytona/workspace/atll-summary && ls /home/daytona/workspace/

~/atll-summary/create_summary.js

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const fs = require('fs');

// ── Color palette ──────────────────────────────────────────────
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                  new Paragraph({ children: [new TextRun({ text: "Adult T-Cell Leukemia / Lymphoma (ATLL)", size: 22, color: MED_BLUE, font: "Calibri" })] })
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                children: [
                  new Paragraph({ alignment: AlignmentType.RIGHT, children: [new TextRun({ text: "Nashik Haematology Service", size: 18, color: DARK_GREY, font: "Calibri" })] }),
                  new Paragraph({ alignment: AlignmentType.RIGHT, children: [new TextRun({ text: "Report Date: 11-Jul-2026", size: 18, color: DARK_GREY, font: "Calibri" })] })
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          new TableCell({
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            margins: { top: 120, bottom: 120, left: 200, right: 200 },
            children: [new Paragraph({
              alignment: AlignmentType.CENTER,
              children: [new TextRun({ text: "⚠  URGENT HAEMATOLOGY-ONCOLOGY REFERRAL REQUIRED  ⚠", bold: true, size: 24, color: WHITE, font: "Calibri" })]
            })]
          })
        ]})]
      }),

      new Paragraph({ spacing: { before: 200, after: 0 }, children: [] }),

      // ── PATIENT DEMOGRAPHICS ──
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          new TableRow({ children: [
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          new TableRow({ children: [
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          new TableRow({ children: [
            cell("Dr. Nilesh Wasekar (DM Haematology)"), cell("Shrinath Hospital, Nashik"), cell("Unipath / Unigenome, Ahmedabad"), cell("11-Jul-2026")
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      // ── DIAGNOSIS ──
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      sectionHeading("2.  Diagnosis"),
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              new Paragraph({ children: [new TextRun({ text: "Primary Diagnosis:", bold: true, size: 22, color: DARK_BLUE, font: "Calibri" })] }),
              new Paragraph({ spacing: { before: 80 }, children: [new TextRun({ text: "Adult T-Cell Leukemia / Lymphoma (ATLL) - Acute Subtype (Most Likely)", bold: true, size: 28, color: RED_ALERT, font: "Calibri" })] }),
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      bodyText("The flow cytometry immunophenotyping (Leukemia/Lymphoma Panel, Unipath) identifies a clonal, mature T-cell neoplasm comprising 74% of the circulating lymphoid cells. The morphological and immunophenotypic features are consistent with ATLL, a high-grade T-cell malignancy driven by HTLV-1 infection."),

      // ── CBC SUMMARY ──
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      sectionHeading("3.  CBC & Peripheral Smear (NHS Diagnostics, 09-Jul-2026)"),
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          new TableRow({ children: [hCell("Parameter"), hCell("Value"), hCell("Reference Range"), hCell("Status")] }),
          new TableRow({ children: [cell("Haemoglobin"), cell("14.2 g/dL"), cell("13.0-17.0"), cell("Normal", { color: "2E7D32" })] }),
          new TableRow({ children: [cell("Total Leucocytes (WBC)"), cell("49,880 /cmm"), cell("4,000-11,000"), cell("HIGH ▲", { bold: true, color: RED_ALERT })] }),
          new TableRow({ children: [cell("Neutrophils"), cell("15.7%  (7,810/cmm abs.)"), cell("40-80%"), cell("LOW ▼", { bold: true, color: AMBER })] }),
          new TableRow({ children: [cell("Lymphocytes"), cell("57.4%  (28,640/cmm abs.)"), cell("20-40%"), cell("HIGH ▲", { bold: true, color: RED_ALERT })] }),
          new TableRow({ children: [cell("Monocytes"), cell("25.4%  (12,690/cmm abs.)"), cell("4-7%"), cell("HIGH ▲", { bold: true, color: AMBER })] }),
          new TableRow({ children: [cell("Platelets"), cell("85,000 /μL"), cell("150,000-450,000"), cell("LOW ▼  (Thrombocytopenia)", { bold: true, color: RED_ALERT })] }),
          new TableRow({ children: [cell("Platelet Distribution Width"), cell("20.3%"), cell("10.0-17.9%"), cell("Elevated", { color: AMBER })] })
        ]
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          new TableCell({
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              new Paragraph({ spacing: { before: 60 }, children: [new TextRun({ text: "57% atypical lymphoid cells with pale cytoplasm and predominantly polar villi. Platelets reduced. No haemoparasites. RBCs normocytic normochromic. Initial morphological impression: Chronic Lymphoproliferative Disorder (? Splenic Marginal Zone Lymphoma). Flow cytometry confirmed T-cell phenotype - B-cell differential excluded.", size: 20, font: "Calibri", color: DARK_GREY })] })
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      // ── FLOW CYTOMETRY ──
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      sectionHeading("4.  Flow Cytometry Immunophenotyping (Unipath, 10-Jul-2026)"),
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          new TableRow({ children: [hCell("Marker"), hCell("Intensity"), hCell("Result"), hCell("Marker"), hCell("Intensity"), hCell("Result")] }),
          new TableRow({ children: [cell("CD45"), cell("Bright"), cell("POSITIVE", { bold: true, color: "2E7D32" }), cell("CD2"), cell("Moderate"), cell("POSITIVE", { bold: true, color: "2E7D32" })] }),
          new TableRow({ children: [cell("CD3"), cell("Bright"), cell("POSITIVE", { bold: true, color: "2E7D32" }), cell("CD5"), cell("Moderate"), cell("POSITIVE", { bold: true, color: "2E7D32" })] }),
          new TableRow({ children: [cell("CD7"), cell("Dim-Moderate"), cell("POSITIVE", { bold: true, color: "2E7D32" }), cell("CD8"), cell("Bright"), cell("POSITIVE", { bold: true, color: "2E7D32" })] }),
          new TableRow({ children: [cell("CD4"), cell("Variable"), cell("POSITIVE (0.65%)", { color: AMBER }), cell("CD25"), cell("Moderate"), cell("POSITIVE", { bold: true, color: "2E7D32" })] }),
          new TableRow({ children: [cell("CD26"), cell("Dim"), cell("POSITIVE", { bold: true, color: "2E7D32" }), cell("CD52"), cell("Moderate (92.69%)"), cell("POSITIVE", { bold: true, color: "2E7D32" })] }),
          new TableRow({ children: [cell("CD19"), cell("-"), cell("Negative"), cell("Kappa / Lambda"), cell("-"), cell("Negative (B-cell markers absent)")] }),
          new TableRow({ children: [cell("CD34"), cell("-"), cell("Negative"), cell("TCRγδ"), cell("-"), cell("Negative")] }),
          new TableRow({ children: [cell("TRBC1"), cell("-"), cell("Negative*"), cell("CD16 / CD56 / CD57"), cell("-"), cell("Negative")] })
        ]
      }),
      new Paragraph({ spacing: { before: 80, after: 40 }, children: [new TextRun({ text: "* TRBC1 negativity (98.47% of cells) confirms clonal T-cell receptor beta-chain expression - diagnostic of clonal T-cell neoplasm.", size: 19, font: "Calibri", color: DARK_GREY, italics: true })] }),

      new Paragraph({ spacing: { before: 120, after: 60 }, children: [new TextRun({ text: "T-Cell Subset Analysis", bold: true, size: 21, color: DARK_BLUE, font: "Calibri" })] }),
      new Table({
        width: { size: 100, type: WidthType.PERCENTAGE },
        borders: thinBorder(),
        rows: [
          new TableRow({ children: [hCell("Parameter"), hCell("Value"), hCell("Significance")] }),
          new TableRow({ children: [cell("CD3+ T-cells"), cell("99.26% of lymphoid gate"), cell("Near-total T-cell expansion")] }),
          new TableRow({ children: [cell("CD8+ (within TCRαβ)"), cell("99.00%"), cell("Dominant CD8+ phenotype (atypical for ATLL)", { color: AMBER })] }),
          new TableRow({ children: [cell("CD4+"), cell("0.65%"), cell("Markedly suppressed normal CD4+ T-helpers")] }),
          new TableRow({ children: [cell("TCRγδ+"), cell("1.11%"), cell("Normal range - not a γδ T-cell lymphoma")] }),
          new TableRow({ children: [cell("NK cells (CD3-/CD56+)"), cell("0.85%"), cell("Near absent")] }),
          new TableRow({ children: [cell("B cells"), cell("0.71%"), cell("Near absent - B-cell lymphoma excluded")] })
        ]
      }),

      // ── IMMUNOTHERAPY TARGET ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("5.  Immunotherapy Target (Lab-Identified)"),
      new Table({
        width: { size: 100, type: WidthType.PERCENTAGE },
        borders: thinBorder(),
        rows: [
          new TableRow({ children: [hCell("Target"), hCell("Clone"), hCell("Expression (%)"), hCell("Drug"), hCell("Status")] }),
          new TableRow({ children: [
            cell("CD52"), cell("ALEMMUT.RMAB"), cell("92.69% of abnormal cells", { bold: true, color: "2E7D32" }), cell("Alemtuzumab (anti-CD52)"), cell("Investigational in ATLL")
          ]})
        ]
      }),
      new Paragraph({ spacing: { before: 80 }, children: [new TextRun({ text: "Note: CD52 expression is high but Alemtuzumab is not standard first-line for ATLL. Discuss in MDT.", size: 19, font: "Calibri", color: DARK_GREY, italics: true })] }),

      // ── DIAGNOSTIC REASONING ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("6.  Diagnostic Reasoning & Differential Diagnosis"),
      bodyText("The combination of findings below supports ATLL as the unifying diagnosis:"),
      bulletText("Markedly elevated WBC with absolute lymphocytosis (ALC ~37,320/cmm per flow report)"),
      bulletText("74% circulating clonal T-cells - small cell, low side scatter morphology"),
      bulletText("Mature T-cell phenotype: CD3+, CD2+, CD5+, CD7+, CD8 bright - all negative for B-cell, NK-cell, and precursor markers"),
      bulletText("CD25 (IL-2 receptor alpha) expression - a hallmark of ATLL malignant T-cells"),
      bulletText("TRBC1 negativity confirms clonality (TCR beta chain clonal rearrangement)"),
      bulletText("Thrombocytopenia (85K) - consistent with bone marrow infiltration"),
      bulletText("Age 56 (fifth-to-seventh decade peak for ATLL)"),

      new Paragraph({ spacing: { before: 140, after: 60 }, children: [new TextRun({ text: "Differentials Considered and Excluded:", bold: true, size: 21, color: DARK_BLUE, font: "Calibri" })] }),
      new Table({
        width: { size: 100, type: WidthType.PERCENTAGE },
        borders: thinBorder(),
        rows: [
          new TableRow({ children: [hCell("Differential"), hCell("Reason Excluded")] }),
          new TableRow({ children: [cell("Splenic Marginal Zone Lymphoma (initial smear impression)"), cell("B-cell neoplasm; CD19 neg, Kappa/Lambda neg - definitively excluded by flow cytometry")] }),
          new TableRow({ children: [cell("T-Prolymphocytic Leukemia (T-PLL)"), cell("T-PLL is typically CD4+ (60%) or CD4+/CD8+; our case is CD8-dominant; CD25 usually negative in T-PLL; TCL1 not tested")] }),
          new TableRow({ children: [cell("Sezary Syndrome / Mycosis Fungoides"), cell("Requires skin biopsy evidence and CD4+ Sezary cells; CD8 dominant here makes it less likely")] }),
          new TableRow({ children: [cell("T-LGL Leukemia"), cell("T-LGL is CD8+/CD57+/CD56+; CD57 and CD56 are negative here; neutropenia not dominant")] }),
          new TableRow({ children: [cell("NK/T-cell Lymphoma"), cell("CD56 negative; TCRγδ negative; EBV-driven - different entity")] })
        ]
      }),
      new Paragraph({ spacing: { before: 80 }, children: [new TextRun({ text: "The CD8-dominant phenotype (99% CD8+) is atypical for classic ATLL (which is usually CD4+CD8-). However, CD8+ ATLL variants are documented and carry comparable or worse prognosis. Confirmation with HTLV-1 serology is essential.", size: 19, font: "Calibri", color: AMBER, italics: true })] }),

      // ── PENDING INVESTIGATIONS ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("7.  Urgent Pending Investigations"),
      new Table({
        width: { size: 100, type: WidthType.PERCENTAGE },
        borders: thinBorder(),
        rows: [
          new TableRow({ children: [hCell("Test"), hCell("Purpose"), hCell("Priority")] }),
          new TableRow({ children: [cell("HTLV-1 Serology (ELISA + Western Blot)"), cell("Confirm causative retrovirus - mandatory for ATLL diagnosis"), cell("URGENT", { bold: true, color: RED_ALERT })] }),
          new TableRow({ children: [cell("HTLV-1 Proviral Load (PCR)"), cell("Quantify viral burden; aids prognosis"), cell("Urgent", { color: RED_ALERT })] }),
          new TableRow({ children: [cell("LDH, Uric Acid, Calcium, Beta-2 Microglobulin"), cell("Staging markers; hypercalcaemia is a hallmark of acute ATLL"), cell("Urgent", { color: RED_ALERT })] }),
          new TableRow({ children: [cell("CT Chest / Abdomen / Pelvis with contrast"), cell("Assess lymphadenopathy, hepatosplenomegaly, organ involvement"), cell("Urgent", { color: RED_ALERT })] }),
          new TableRow({ children: [cell("Bone Marrow Aspirate & Trephine Biopsy"), cell("Assess marrow infiltration; staging"), cell("Urgent", { color: RED_ALERT })] }),
          new TableRow({ children: [cell("Cytogenetics / FISH / Molecular Panel"), cell("Complex karyotype common in ATLL; CCR4 mutation (prognostic)"), cell("High Priority", { color: AMBER })] }),
          new TableRow({ children: [cell("TCR Gene Rearrangement (Southern blot or PCR)"), cell("Confirm clonality at molecular level"), cell("High Priority", { color: AMBER })] }),
          new TableRow({ children: [cell("Serum Albumin, BUN (renal function)"), cell("Elevated BUN + low albumin = unfavourable chronic ATLL prognosis"), cell("Standard")] }),
          new TableRow({ children: [cell("HTLV-1 PCR on CSF (if neurological symptoms)"), cell("Exclude CNS involvement / HAM-TSP"), cell("As indicated")] })
        ]
      }),

      // ── SUBTYPE & PROGNOSIS ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("8.  ATLL Subtype Classification (Shimoyama) & Prognosis"),
      new Table({
        width: { size: 100, type: WidthType.PERCENTAGE },
        borders: thinBorder(),
        rows: [
          new TableRow({ children: [hCell("Subtype"), hCell("Key Features"), hCell("Proportion"), hCell("Median OS")] }),
          new TableRow({
            children: [
              new TableCell({
                shading: { fill: "FDECEA", type: ShadingType.CLEAR, color: "auto" },
                margins: { top: 80, bottom: 80, left: 120, right: 120 },
                children: [new Paragraph({ children: [new TextRun({ text: "Acute  ← LIKELY", bold: true, size: 20, color: RED_ALERT, font: "Calibri" })] })]
              }),
              cell("High WBC, hypercalcaemia, LDH elevation, skin lesions, circulating leukemic cells"),
              cell("~55%"),
              cell("< 1 year without alloHCT", { bold: true, color: RED_ALERT })
            ]
          }),
          new TableRow({ children: [cell("Lymphoma"), cell("Lymphadenopathy dominant; WBC normal or mildly elevated"), cell("~20%"), cell("< 1 year")] }),
          new TableRow({ children: [cell("Chronic"), cell("Moderate lymphocytosis, skin involvement; slower course"), cell("~20%"), cell("~2 years")] }),
          new TableRow({ children: [cell("Smoldering"), cell("Low WBC, skin/lung involvement; indolent"), cell("~5%"), cell(">5 years")] })
        ]
      }),
      new Paragraph({ spacing: { before: 80 }, children: [new TextRun({ text: "Prognostic factors conferring adverse outcome in acute ATLL: age >40, PS ≥2, hypercalcaemia, elevated LDH, ≥4 involved lesions, high BUN, low albumin.", size: 19, font: "Calibri", color: DARK_GREY, italics: true })] }),

      // ── TREATMENT ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("9.  Treatment Framework (Per Current Evidence)"),
      bodyText("Treatment is determined by ATLL subtype, HTLV-1 confirmation, patient fitness (ECOG PS), and intent for allogeneic haematopoietic cell transplantation (alloHCT)."),

      new Paragraph({ spacing: { before: 120, after: 60 }, children: [new TextRun({ text: "Acute / Lymphoma ATLL (Aggressive Subtypes):", bold: true, size: 21, color: DARK_BLUE, font: "Calibri" })] }),
      bulletText("First-line: VCAP-AMP-VECP (Japan) or CHOP-based regimens (Western centres)"),
      bulletText("Mogamulizumab (anti-CCR4) approved in Japan and USA for relapsed/refractory ATLL; CCR4 expression >90% in ATLL"),
      bulletText("Allogeneic HCT: Only potentially curative option; 3-year OS ~30-40% in transplanted patients"),
      subBullet("Refer for HLA typing and donor search early if patient is transplant-eligible"),
      bulletText("Brentuximab vedotin (if CD30+), Pralatrexate, Romidepsin - alternative agents for relapsed disease"),
      bulletText("Lenalidomide: Active in relapsed ATLL; being studied in combination regimens"),

      new Paragraph({ spacing: { before: 120, after: 60 }, children: [new TextRun({ text: "Smoldering / Chronic ATLL (Indolent Subtypes):", bold: true, size: 21, color: DARK_BLUE, font: "Calibri" })] }),
      bulletText("Antiviral: Zidovudine 500-1000 mg/day + Interferon-alpha 6-9 MU - improves 5-year survival in indolent disease"),
      bulletText("Watch-and-wait acceptable for truly asymptomatic smoldering type"),
      bulletText("~50% transform to aggressive disease at median 18 months - close surveillance mandatory"),

      // ── SUMMARY BOX ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("10.  Clinical Summary & Action Points"),
      new Table({
        width: { size: 100, type: WidthType.PERCENTAGE },
        borders: thinBorder(),
        rows: [new TableRow({ children: [
          new TableCell({
            shading: { fill: LIGHT_BLUE, type: ShadingType.CLEAR, color: "auto" },
            margins: { top: 140, bottom: 140, left: 200, right: 200 },
            children: [
              new Paragraph({ spacing: { before: 0, after: 80 }, children: [new TextRun({ text: "Mr. Rajendra Dagu Nagare, 56M, presents with lymphocytosis (WBC ~50,000/cmm) and thrombocytopenia. Peripheral smear showed atypical lymphoid cells initially suggesting SMZL. Flow cytometry (10-colour panel) identifies a 74% clonal, mature T-cell population expressing CD3, CD2, CD5, CD7, CD8, CD25, CD26, and CD52, with absent B-cell and NK-cell markers. TRBC1 negativity confirms clonal T-cell receptor rearrangement.", size: 20, font: "Calibri", color: DARK_GREY })] }),
              new Paragraph({ spacing: { before: 60, after: 80 }, children: [new TextRun({ text: "The immunophenotype is consistent with Adult T-Cell Leukemia/Lymphoma (ATLL), most likely acute subtype. HTLV-1 serology is mandatorily required to confirm the diagnosis. The CD8-dominant phenotype (unusual for ATLL) warrants specialist review but does not exclude ATLL.", size: 20, font: "Calibri", color: DARK_GREY })] }),
              new Paragraph({ spacing: { before: 60, after: 40 }, children: [new TextRun({ text: "Immediate action steps:", bold: true, size: 21, color: DARK_BLUE, font: "Calibri" })] }),
              new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text: "Send HTLV-1 ELISA serology TODAY", bold: true, size: 20, color: RED_ALERT, font: "Calibri" })] }),
              new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text: "Order serum calcium, LDH, uric acid, B2M, albumin, renal function", size: 20, font: "Calibri", color: DARK_GREY })] }),
              new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text: "Arrange urgent CT chest/abdomen/pelvis", size: 20, font: "Calibri", color: DARK_GREY })] }),
              new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text: "Plan bone marrow biopsy for staging", size: 20, font: "Calibri", color: DARK_GREY })] }),
              new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text: "Urgent haematology-oncology referral / MDT discussion", bold: true, size: 20, color: RED_ALERT, font: "Calibri" })] }),
              new Paragraph({ bullet: { level: 0 }, children: [new TextRun({ text: "If transplant-eligible: initiate HLA typing and donor search early", size: 20, font: "Calibri", color: DARK_GREY })] })
            ]
          })
        ]})]
      }),

      // ── REFERENCES ──
      new Paragraph({ spacing: { before: 240, after: 0 }, children: [] }),
      sectionHeading("References"),
      bodyText("1. Goldman-Cecil Medicine International Edition (26th Ed). Chapter 360: HTLV-1 and ATLL."),
      bodyText("2. Harrison's Principles of Internal Medicine, 22nd Edition (2025). Chapter: Human T-Cell Lymphotropic Virus."),
      bodyText("3. Henry's Clinical Diagnosis and Management by Laboratory Methods. Chapter 34: T-Cell Neoplasms."),
      bodyText("4. Stuver R, Horwitz SM, Epstein-Peterson ZD. Treatment of Adult T-Cell Leukemia/Lymphoma. Curr Treat Options Oncol. 2023 Aug. PMID: 37300656."),
      bodyText("5. Letafati A et al. Therapeutic approaches for HTLV-1-associated adult T-cell leukemia/lymphoma. Med Oncol. 2023. PMID: 37689806."),

      new Paragraph({ spacing: { before: 160 }, children: [new TextRun({ text: "Disclaimer: This report is a clinical decision-support summary generated from laboratory data provided. It does not replace specialist medical judgment. Final diagnosis must integrate clinical findings, HTLV-1 serology, and additional investigations.", size: 18, font: "Calibri", color: "888888", italics: true })] })
    ]
  }]
});

Packer.toBuffer(doc).then(buffer => {
  fs.writeFileSync('/home/daytona/workspace/atll-summary/ATLL_Clinical_Summary_Rajendra_Nagare.docx', buffer);
  console.log('Document created successfully.');
}).catch(err => {
  console.error('Error:', err);
  process.exit(1);
});

cd /home/daytona/workspace/atll-summary && node create_summary.js 2>&1

python3 /home/daytona/skills/docx/scripts/office/validate.py /home/daytona/works…

python3 -c "import zipfile; z = zipfile.ZipFile('/home/daytona/workspace/atll-su…

ls -lh /home/daytona/workspace/atll-summary/