ALL FOUR LEUKEMIAS - Comprehensive Comparative Chart (MBBS)

"""
Leukemia Diagnostic Flowchart - Excel Generator
Produces a rich .xlsx with:
  Sheet 1 - Visual Diagnostic Flowchart (cell-drawn with borders/fills/arrows)
  Sheet 2 - Comprehensive Comparison Table
  Sheet 3 - Quick Reference Card
"""

from openpyxl import Workbook
from openpyxl.styles import (
    PatternFill, Font, Alignment, Border, Side, GradientFill
)
from openpyxl.utils import get_column_letter
from openpyxl.styles.numbers import FORMAT_TEXT
import openpyxl

wb = Workbook()

# ─────────────────────────────────────────────────────────
# HELPERS
# ─────────────────────────────────────────────────────────

def hex_fill(hex_color):
    return PatternFill("solid", fgColor=hex_color)

def thin_border(top=True, bottom=True, left=True, right=True):
    s = Side(style="thin", color="000000")
    n = Side(style=None)
    return Border(
        top=s if top else n,
        bottom=s if bottom else n,
        left=s if left else n,
        right=s if right else n,
    )

def thick_border():
    s = Side(style="medium", color="000000")
    return Border(top=s, bottom=s, left=s, right=s)

def center(wrap=False):
    return Alignment(horizontal="center", vertical="center", wrap_text=wrap)

def left_align(wrap=True):
    return Alignment(horizontal="left", vertical="center", wrap_text=wrap)

def bold_font(size=10, color="000000"):
    return Font(name="Arial", bold=True, size=size, color=color)

def regular_font(size=9, color="000000"):
    return Font(name="Arial", size=size, color=color)

def merge_write(ws, r1, c1, r2, c2, value, fill=None, font=None, align=None, border=None):
    ws.merge_cells(start_row=r1, start_column=c1, end_row=r2, end_column=c2)
    cell = ws.cell(row=r1, column=c1)
    cell.value = value
    if fill:   cell.fill = fill
    if font:   cell.font = font
    if align:  cell.alignment = align
    if border:
        for row in ws.iter_rows(min_row=r1, max_row=r2, min_col=c1, max_col=c2):
            for c in row:
                c.border = border
    return cell

def arrow_cell(ws, row, col, direction="down"):
    c = ws.cell(row=row, column=col)
    c.value = "▼" if direction == "down" else ("▶" if direction == "right" else "◀")
    c.font = Font(name="Arial", size=14, bold=True, color="444444")
    c.alignment = center()

# ─────────────────────────────────────────────────────────
# COLOR PALETTE
# ─────────────────────────────────────────────────────────
TITLE_BG     = "1A3C5E"   # dark navy
TITLE_FG     = "FFFFFF"

START_BG     = "2E86AB"   # teal - start node
DECISION_BG  = "F6AE2D"   # amber - decision diamonds
ALL_BG       = "E63946"   # red - ALL
AML_BG       = "FF6B35"   # orange - AML
CML_BG       = "2DC653"   # green - CML
CLL_BG       = "8338EC"   # purple - CLL
LABEL_BG     = "F0F4F8"   # light grey - label rows
HEADER_BG    = "1A3C5E"   # same as title
YES_BG       = "D4EDDA"   # light green yes
NO_BG        = "FDECEA"   # light red no

SEC_ALL      = "FADBD8"
SEC_AML      = "FDEBD0"
SEC_CML      = "D5F5E3"
SEC_CLL      = "E8DAEF"

# ══════════════════════════════════════════════════════════
# SHEET 1 – DIAGNOSTIC FLOWCHART
# ══════════════════════════════════════════════════════════
ws1 = wb.active
ws1.title = "Diagnostic Flowchart"

# Column widths
col_widths = {1:2, 2:18, 3:3, 4:18, 5:3, 6:18, 7:3, 8:18, 9:2}
for col, w in col_widths.items():
    ws1.column_dimensions[get_column_letter(col)].width = w

# Row heights (will set dynamically)
def set_row_heights(ws, heights_dict):
    for r, h in heights_dict.items():
        ws.row_dimensions[r].height = h

# ── TITLE ──
merge_write(ws1, 1, 1, 2, 9,
    "LEUKEMIA DIAGNOSTIC FLOWCHART  |  ALL • AML • CML • CLL",
    fill=hex_fill(TITLE_BG),
    font=Font(name="Arial", bold=True, size=14, color=TITLE_FG),
    align=center(wrap=False),
    border=thick_border()
)

# ── START NODE ──
merge_write(ws1, 4, 3, 5, 7,
    "🔬  PATIENT PRESENTATION\nSuspected Leukemia",
    fill=hex_fill(START_BG),
    font=Font(name="Arial", bold=True, size=11, color="FFFFFF"),
    align=center(wrap=True),
    border=thick_border()
)
arrow_cell(ws1, 6, 5)

# ── DECISION 1: ACUTE vs CHRONIC ──
merge_write(ws1, 7, 3, 8, 7,
    "◆  ONSET & BLOOD FILM\nAre blasts >20% in blood/marrow?",
    fill=hex_fill(DECISION_BG),
    font=Font(name="Arial", bold=True, size=10, color="1A1A1A"),
    align=center(wrap=True),
    border=thick_border()
)

# YES / NO labels
merge_write(ws1, 9, 2, 9, 4, "YES  ▼  (Blasts ≥20%)",
    fill=hex_fill(YES_BG), font=bold_font(9, "1A6B31"), align=center())
merge_write(ws1, 9, 6, 9, 8, "NO  ▼  (Blasts <20%, mature cells)",
    fill=hex_fill(NO_BG), font=bold_font(9, "8B0000"), align=center())

arrow_cell(ws1, 10, 3)
arrow_cell(ws1, 10, 7)

# ── DECISION 2a: ACUTE - Lineage ──
merge_write(ws1, 11, 2, 12, 4,
    "◆  LINEAGE\nAre cells lymphoid?\n(TdT+, CD10+, CD19/CD3+)",
    fill=hex_fill(DECISION_BG),
    font=Font(name="Arial", bold=True, size=9, color="1A1A1A"),
    align=center(wrap=True),
    border=thick_border()
)

# ── DECISION 2b: CHRONIC - Lineage ──
merge_write(ws1, 11, 6, 12, 8,
    "◆  Philadelphia Chromosome?\nt(9;22) BCR-ABL1\n(FISH / PCR)",
    fill=hex_fill(DECISION_BG),
    font=Font(name="Arial", bold=True, size=9, color="1A1A1A"),
    align=center(wrap=True),
    border=thick_border()
)

# YES/NO for acute lineage
merge_write(ws1, 13, 2, 13, 2, "YES ▼", fill=hex_fill(YES_BG), font=bold_font(8,"1A6B31"), align=center())
merge_write(ws1, 13, 4, 13, 4, "NO ▼", fill=hex_fill(NO_BG), font=bold_font(8,"8B0000"), align=center())
# YES/NO for chronic Philadelphia
merge_write(ws1, 13, 6, 13, 6, "YES ▼", fill=hex_fill(YES_BG), font=bold_font(8,"1A6B31"), align=center())
merge_write(ws1, 13, 8, 13, 8, "NO ▼", fill=hex_fill(NO_BG), font=bold_font(8,"8B0000"), align=center())

# ── DIAGNOSIS BOXES ──
# ALL
merge_write(ws1, 15, 1, 22, 3,
    "✦  ALL\nAcute Lymphoblastic Leukemia\n\n"
    "Age: Children (peak 3 yrs)\n"
    "Cells: Lymphoblasts\n"
    "TdT: POSITIVE ✓\n"
    "CD10 (CALLA): + \n"
    "CD19/CD3: +\n"
    "Smear: Lymphoblasts\n"
    "Chromosomes:\n  t(12;21) = best\n  t(9;22) = worst\n\n"
    "Rx: Vincristine +\nPrednisolone +\nL-Asparaginase\n(+TKI if Ph+)\n\n"
    "⚠ CNS prophylaxis\nmandatory!",
    fill=hex_fill(ALL_BG),
    font=Font(name="Arial", bold=True, size=9, color="FFFFFF"),
    align=Alignment(horizontal="left", vertical="top", wrap_text=True),
    border=thick_border()
)

# AML
merge_write(ws1, 15, 4, 22, 5,
    "✦  AML\nAcute Myeloid Leukemia\n\n"
    "Age: Adults (>60 yr)\n"
    "Cells: Myeloblasts\n"
    "TdT: Negative ✗\n"
    "MPO: POSITIVE ✓\n"
    "Auer Rods: ✓ (pathognomonic)\n"
    "CD13, CD33, CD117: +\n\n"
    "Key subtype:\nM3-APL → t(15;17)\nRx: ATRA + Arsenic\n(DIC risk!)\n\n"
    "Others:\n'7+3' regimen\n(Cytarabine +\nAnthracycline)",
    fill=hex_fill(AML_BG),
    font=Font(name="Arial", bold=True, size=9, color="FFFFFF"),
    align=Alignment(horizontal="left", vertical="top", wrap_text=True),
    border=thick_border()
)

# CML
merge_write(ws1, 15, 6, 22, 7,
    "✦  CML\nChronic Myeloid Leukemia\n\n"
    "Age: 40-60 yrs\n"
    "Cells: Full myeloid spectrum\n"
    "Ph chromosome: POSITIVE ✓\n"
    "BCR-ABL1 p210\n"
    "LAP score: LOW ✓\n"
    "Smear: Myelocyte bulge\n+ Basophilia\n+ Thrombocytosis\n\n"
    "Phases:\nChronic → Accelerated\n→ Blast Crisis\n\n"
    "Rx: Imatinib (TKI)\nDasatinib/Nilotinib",
    fill=hex_fill(CML_BG),
    font=Font(name="Arial", bold=True, size=9, color="FFFFFF"),
    align=Alignment(horizontal="left", vertical="top", wrap_text=True),
    border=thick_border()
)

# CLL
merge_write(ws1, 15, 8, 22, 9,
    "✦  CLL\nChronic Lymphocytic Leukemia\n\n"
    "Age: Elderly (>65 yr)\n"
    "Cells: Mature B lymphocytes\n"
    "Ph chromosome: Negative ✗\n"
    "CD5+, CD19+, CD23+\n"
    "Smear: Smudge cells ✓\n"
    "(pathognomonic)\n\n"
    "Often asymptomatic\nRai / Binet staging\n\n"
    "Rx: Watch & wait\n→ BTK inhibitors\n(Ibrutinib)\n→ Venetoclax\n→ Rituximab",
    fill=hex_fill(CLL_BG),
    font=Font(name="Arial", bold=True, size=9, color="FFFFFF"),
    align=Alignment(horizontal="left", vertical="top", wrap_text=True),
    border=thick_border()
)

# ── KEY DIFFERENTIATORS ROW ──
merge_write(ws1, 23, 1, 23, 9,
    "KEY DIFFERENTIATORS AT A GLANCE",
    fill=hex_fill(HEADER_BG),
    font=Font(name="Arial", bold=True, size=10, color="FFFFFF"),
    align=center()
)

diff_data = [
    ("Test", "ALL", "AML", "CML", "CLL"),
    ("TdT", "✓ POSITIVE", "✗ Negative", "✗ Negative", "✗ Negative"),
    ("MPO / Auer Rods", "✗ Negative", "✓ POSITIVE", "✗ Negative", "✗ Negative"),
    ("Philadelphia chr t(9;22)", "Only in Ph+ ALL (poor Px)", "Rare", "✓ HALLMARK", "✗ Negative"),
    ("LAP Score", "Normal/High", "Normal/High", "✓ LOW", "Normal"),
    ("Smudge Cells", "✗ Absent", "✗ Absent", "✗ Absent", "✓ PRESENT"),
    ("Blasts in marrow", "≥20% lymphoblasts", "≥20% myeloblasts", "<10% chronic phase", "Rare"),
    ("CD5 expression", "✗ Negative", "✗ Negative", "✗ Negative", "✓ POSITIVE"),
    ("Age peak", "Children (3 yr)", "Adults (>60 yr)", "Adults (40-60 yr)", "Elderly (>65 yr)"),
    ("Splenomegaly", "Moderate", "Moderate", "MASSIVE ✓", "Moderate"),
    ("Prognosis", "Children: EXCELLENT", "MODERATE", "GOOD (with TKI)", "INDOLENT (variable)"),
]

col_fills = [LABEL_BG, SEC_ALL, SEC_AML, SEC_CML, SEC_CLL]
col_fgs   = ["1A3C5E", ALL_BG, AML_BG, "1A5E3C", "5B0AAB"]

for i, row_data in enumerate(diff_data):
    row_num = 24 + i
    for j, val in enumerate(row_data):
        cols = [1, 2, 4, 6, 8]
        col_spans = [(1,2), (2,3), (4,5), (6,7), (8,9)]
        ws1.merge_cells(start_row=row_num, start_column=col_spans[j][0],
                        end_row=row_num, end_column=col_spans[j][1])
        c = ws1.cell(row=row_num, column=col_spans[j][0])
        c.value = val
        if i == 0:
            c.fill = hex_fill(HEADER_BG)
            c.font = Font(name="Arial", bold=True, size=9, color="FFFFFF")
        else:
            c.fill = hex_fill(col_fills[j])
            is_pos = "✓" in val or "POSITIVE" in val or "HALLMARK" in val or "PRESENT" in val or "MASSIVE" in val or "EXCELLENT" in val
            is_neg = "✗" in val or "Negative" in val or "Rare" in val
            if j == 0:
                c.font = Font(name="Arial", bold=True, size=9, color="1A3C5E")
            elif is_pos:
                c.font = Font(name="Arial", bold=True, size=9, color="1A5E2A")
            elif is_neg:
                c.font = Font(name="Arial", size=9, color="8B0000")
            else:
                c.font = Font(name="Arial", size=9, color="1A1A1A")
        c.alignment = center(wrap=True)
        c.border = thin_border()

# Row heights
rh = {1:20, 2:20, 3:8, 4:20, 5:20, 6:15,
      7:25, 8:25, 9:18, 10:15, 11:30, 12:30,
      13:15, 14:8}
for r in range(15, 23):
    rh[r] = 16
for r in range(23, 36):
    rh[r] = 20
rh[23] = 22
set_row_heights(ws1, rh)

# ── FOOTNOTE ──
merge_write(ws1, 35, 1, 35, 9,
    "Source: Robbins & Cotran Pathologic Basis of Disease | Goldman-Cecil Medicine | Quick Compendium of Clinical Pathology  |  For MBBS/MD exam use",
    fill=hex_fill("E8EDF2"),
    font=Font(name="Arial", italic=True, size=8, color="666666"),
    align=center()
)


# ══════════════════════════════════════════════════════════
# SHEET 2 – COMPREHENSIVE COMPARISON TABLE
# ══════════════════════════════════════════════════════════
ws2 = wb.create_sheet("Comparison Table")

# Column widths
ws2.column_dimensions["A"].width = 22
ws2.column_dimensions["B"].width = 28
ws2.column_dimensions["C"].width = 28
ws2.column_dimensions["D"].width = 28
ws2.column_dimensions["E"].width = 28

# Title
merge_write(ws2, 1, 1, 2, 5,
    "COMPREHENSIVE LEUKEMIA COMPARISON TABLE  —  MBBS / MD Reference",
    fill=hex_fill(TITLE_BG),
    font=Font(name="Arial", bold=True, size=13, color="FFFFFF"),
    align=center(),
    border=thick_border()
)

# Headers
headers = ["PARAMETER", "ALL", "AML", "CML", "CLL"]
header_fills = [HEADER_BG, ALL_BG, AML_BG, CML_BG, CLL_BG]
for i, (h, hf) in enumerate(zip(headers, header_fills)):
    c = ws2.cell(row=3, column=i+1)
    c.value = h
    c.fill = hex_fill(hf)
    c.font = Font(name="Arial", bold=True, size=10, color="FFFFFF")
    c.alignment = center(wrap=True)
    c.border = thin_border()
ws2.row_dimensions[3].height = 24

# Data rows: (section_header_bool, parameter, ALL, AML, CML, CLL)
rows = [
    # ── SECTION: BASIC ──
    (True, "BASIC CLASSIFICATION", "", "", "", ""),
    (False, "Full Name", "Acute Lymphoblastic Leukemia", "Acute Myeloid Leukemia", "Chronic Myeloid Leukemia", "Chronic Lymphocytic Leukemia"),
    (False, "Cell of Origin", "Immature B or T lymphoblast", "Immature myeloblast (myeloid precursor)", "Pluripotent stem cell → myeloid lineage", "Mature B lymphocyte"),
    (False, "Acute / Chronic", "ACUTE", "ACUTE", "CHRONIC", "CHRONIC"),
    (False, "Myeloid / Lymphoid", "LYMPHOID", "MYELOID", "MYELOID", "LYMPHOID"),

    # ── SECTION: EPIDEMIOLOGY ──
    (True, "EPIDEMIOLOGY", "", "", "", ""),
    (False, "Peak Age", "Children (3 yrs); adults possible", "Adults >60 yrs (most common)", "Middle age 40-60 yrs", "Elderly; median age 70 yrs"),
    (False, "Sex", "Boys > Girls (slight)", "M = F", "M slightly > F", "M:F = 2:1"),
    (False, "Incidence rank", "Most common childhood cancer", "Most common acute leukemia in adults", "15-20% of all adult leukemias", "Most common leukemia in Western world"),
    (False, "Race", "Higher in Hispanic/Latino children", "All races", "All races", "Rare in Asians/Pacific Islanders"),

    # ── SECTION: ETIOLOGY ──
    (True, "ETIOLOGY & GENETICS", "", "", "", ""),
    (False, "Key Chromosomal Abnormality", "t(12;21) ETV6-RUNX1 (25%, best Px)\nt(9;22) BCR-ABL1 (Ph+, poor Px)\nt(4;11) KMT2A (worst Px)\nHyperploidy >50 chr (good Px)", "t(15;17) PML-RARA → APL-M3\nt(8;21) RUNX1-RUNX1T1\ninv(16) CBFB-MYH11\nNPM1, FLT3-ITD mutations", "t(9;22) Philadelphia chromosome\nBCR-ABL1 → p210 fusion protein\n(MANDATORY for diagnosis)", "Del 13q14 (most common, favorable)\nDel 17p TP53 (worst)\nDel 11q ATM\nTrisomy 12"),
    (False, "Key Mutations", "NOTCH1 (T-ALL)\nPAX5, ETV6, RUNX1 (B-ALL)", "NPM1, CEBPA (favorable)\nFLT3-ITD (poor)\nRunX1 (poor)", "BCR-ABL1 kinase domain mutations\n→ TKI resistance", "ATM, NOTCH1, TP53, IGHV mutation status"),
    (False, "Risk Factors", "Down syndrome, ionizing radiation\nPrior chemotherapy", "Down syndrome, prior chemo/radiation\nMyelodysplastic syndrome\nAlkylating agents", "Ionizing radiation\n(cause often unknown)", "Pesticides, Agent Orange\n1st-degree relatives (5-8x risk)"),

    # ── SECTION: CLINICAL ──
    (True, "CLINICAL FEATURES", "", "", "", ""),
    (False, "Onset", "Abrupt (days-weeks)", "Abrupt (days-weeks)", "Insidious (months)", "Very insidious (years); often incidental"),
    (False, "Key Symptoms", "Fever, fatigue, pallor\nBone pain (children)\nLymphadenopathy", "Fatigue, bleeding gums\nInfection, petechiae\nGum hypertrophy (M5)", "Fatigue, weight loss\nEarly satiety (splenomegaly)\nNight sweats", "Often asymptomatic\nFatigue, weight loss\nFrequent infections"),
    (False, "Splenomegaly", "Moderate", "Moderate", "MASSIVE (hallmark)", "Moderate (50-60%)"),
    (False, "Lymphadenopathy", "Common", "Less common", "Uncommon in chronic phase", "Generalized (50-60%)"),
    (False, "CNS Involvement", "COMMON → prophylaxis mandatory", "Less common", "Rare in chronic phase", "Rare"),
    (False, "Mediastinal Mass", "T-ALL: anterior mediastinal mass (thymic)", "No", "No", "No"),
    (False, "Gum Hypertrophy", "Rare", "M4/M5 (monocytic subtype) ✓", "No", "No"),
    (False, "Hepatomegaly", "Common", "Common", "Moderate", "Moderate (50-60%)"),

    # ── SECTION: LAB ──
    (True, "LABORATORY FINDINGS", "", "", "", ""),
    (False, "WBC Count", "Variable; can be very high or low", "Variable; often elevated blasts", "MARKEDLY elevated\n(myeloid spectrum)", "Lymphocytosis ≥5×10⁹/L for ≥3 months"),
    (False, "Peripheral Smear", "Lymphoblasts\n(large nuclei, prominent nucleoli)", "Myeloblasts\nAUER RODS (pathognomonic)\nMPO-positive granules", "Full myeloid spectrum\nMyelocyte BULGE\nBasophilia + Eosinophilia", "Small mature lymphocytes\nSMUDGE CELLS (pathognomonic)"),
    (False, "Anemia", "Yes (marrow replacement)", "Yes (marrow replacement)", "Mild initially", "Mild; AIHA in 10-15%"),
    (False, "Platelets", "Thrombocytopenia ↓", "Thrombocytopenia ↓", "Thrombocytosis ↑ (early)", "Thrombocytopenia ↓ (late/autoimmune)"),
    (False, "LAP Score", "Normal / High", "Normal / High", "LOW ← key differentiator", "Normal"),
    (False, "Bone Marrow Blasts", "≥20% lymphoblasts", "≥20% myeloblasts", "<10% (chronic phase)", "Rare lymphocytes"),
    (False, "Serum LDH", "Often elevated", "Often elevated", "Often elevated", "May be elevated"),
    (False, "Uric Acid", "Elevated (tumor lysis risk)", "Elevated (tumor lysis risk)", "Elevated", "Mildly elevated"),

    # ── SECTION: IMMUNOPHENOTYPE ──
    (True, "IMMUNOPHENOTYPE", "", "", "", ""),
    (False, "Key Positive Markers", "TdT ✓ (hallmark)\nCD10 (CALLA) ✓\nCD19, CD20 (B-ALL)\nCD3, CD7 (T-ALL)", "MPO ✓\nCD13, CD33, CD117 ✓\nCD34 (immature)\nCD14 (monocytic subtypes)", "CD13, CD33 (myeloid)\nCD34 (immature precursors)", "CD5 ✓\nCD19 ✓\nCD23 ✓\nCD20 (weak)\nWeak surface Ig"),
    (False, "TdT", "POSITIVE (hallmark)", "Negative", "Negative", "Negative"),
    (False, "Special Cytochemistry", "PAS positive (clumpy blocks)\nMPO Negative", "MPO POSITIVE ✓\nSudan Black B positive\nNSE positive (M4/M5)", "MPO positive (myeloid cells)\nLAP LOW", "PAS positive (diffuse)\nMPO negative"),

    # ── SECTION: DIAGNOSIS CRITERIA ──
    (True, "DIAGNOSTIC CRITERIA", "", "", "", ""),
    (False, "WHO Blast Threshold", "≥20% lymphoblasts in marrow/blood", "≥20% myeloblasts in marrow/blood", "Philadelphia chromosome required\n(no blast threshold for chronic phase)", "Absolute B-lymphocyte count\n≥5×10⁹/L for ≥3 months"),
    (False, "Gold Standard Test", "Bone marrow biopsy + Immunophenotyping\n(Flow cytometry)", "Bone marrow biopsy + Cytochemistry\n(MPO stain) + Cytogenetics", "FISH / PCR for BCR-ABL1\nPhiladelphia chromosome", "Flow cytometry (CD5+/CD19+/CD23+)\n+ peripheral blood count"),
    (False, "Key Diagnostic Finding", "TdT+ lymphoblasts ≥20%", "Auer rods in myeloblasts", "Philadelphia chromosome t(9;22)", "Smudge cells + CD5+/CD19+/CD23+ B cells"),

    # ── SECTION: STAGING ──
    (True, "STAGING / PHASES", "", "", "", ""),
    (False, "Staging System", "Induction → Consolidation\n→ Maintenance", "Induction → Consolidation\n(no maintenance in most protocols)", "Sokal / EUTOS risk score\n(Chronic → Accelerated → Blast Crisis)", "Rai Staging (0-IV)\nBinet Staging (A/B/C)"),
    (False, "Disease Phases", "Relapse most common in marrow, CNS, testes", "De-novo or secondary (post-MDS)\nM0-M7 FAB classification", "Chronic phase (low blasts)\nAccelerated: blasts 10-19%\nBlast crisis: blasts ≥20%", "Indolent → Progressive\nRichter transformation (5-10%)\n→ Aggressive DLBCL"),
    (False, "Blast Crisis (CML)", "—", "—", "Blasts ≥20%; AML-type (70%)\nor ALL-type (30%)", "—"),

    # ── SECTION: TREATMENT ──
    (True, "TREATMENT", "", "", "", ""),
    (False, "First-Line Induction", "Vincristine + Prednisolone\n+ L-Asparaginase\n+ Anthracycline (VPDL)", "'7+3' regimen:\nCytarabine (7 days)\n+ Anthracycline (3 days)", "Imatinib (Gleevec) 400 mg/day\n→ 1st-line TKI\n(Dasatinib or Nilotinib: 2nd gen)", "Watch and Wait if asymptomatic\nBTK inhibitor: Ibrutinib\nBCL-2 inhibitor: Venetoclax\nAnti-CD20: Rituximab"),
    (False, "Special/Targeted Rx", "Ph+ ALL: Add imatinib/dasatinib\nAlloSCT in high-risk", "APL-M3: ATRA + Arsenic trioxide\n(highly effective, avoid DIC)\nGemtuzumab ozogamicin", "Ponatinib for T315I mutation\nAlloSCT in blast crisis", "Chemoimmunotherapy: FCR\n(Fludarabine + Cyclophosphamide\n+ Rituximab) for fit patients"),
    (False, "CNS Prophylaxis", "MANDATORY\n(Intrathecal methotrexate)", "Selective", "Not routine", "Not routine"),
    (False, "Maintenance Therapy", "Yes (6-mercaptopurine +\nMethotrexate × 2-3 yrs)", "Generally not used", "Indefinite TKI (lifelong)", "Only when disease progresses"),
    (False, "Stem Cell Transplant", "High-risk relapsed ALL", "AML in CR1 (high-risk)", "Blast crisis; TKI-resistant CML", "Refractory/relapsed CLL"),

    # ── SECTION: PROGNOSIS ──
    (True, "PROGNOSIS", "", "", "", ""),
    (False, "Overall Survival", "Children: ~90% cure\nAdults: 40-50% cure", "Younger adults: 40-50% long-term\nElderly: <20% 5-yr OS", "Excellent with TKI\n(near-normal life expectancy)", "Indolent; median survival ~10 yr\n(range: 1-30+ yr)"),
    (False, "Good Prognostic Factors", "Age 1-10 yr\nWBC <10,000\nt(12;21) ETV6-RUNX1\nHyperploidy >50 chr\nFemale sex", "t(15;17), t(8;21), inv(16)\nYoung age (<60 yr)\nNPM1 mutation (without FLT3)\nCEBPA biallelic", "Chronic phase at diagnosis\nLow Sokal score\nCCyR / MMR with TKI\nYoung age", "Rai 0\nMutated IGHV\nDel 13q only\nNo del 17p/11q\nZAP-70 negative"),
    (False, "Poor Prognostic Factors", "Age <1 yr or adult\nWBC >100,000\nt(9;22), t(4;11)\nHypoploidy\nMale sex (T-ALL)", "Complex karyotype\nFLT3-ITD mutation\nTP53 mutation\nAge >60 yr\nSecondary AML (post-MDS)", "Blast crisis\nDel 17p / ABL kinase mutations\nHigh Sokal score\nTKI resistance", "Del 17p (TP53) - worst\nDel 11q (ATM)\nUnmutated IGHV\nZAP-70+, CD38+\nRichter transformation"),
    (False, "Transformation Risk", "Relapse possible; CNS relapse", "Secondary MDS/AML post-chemo", "Blast crisis (AML or ALL type)\n~3-5%/yr untreated", "Richter syndrome → DLBCL (5-10%)"),
]

# Write rows
row_fills = {
    "ALL": SEC_ALL, "AML": SEC_AML, "CML": SEC_CML, "CLL": SEC_CLL
}

current_row = 4
for is_section, param, all_v, aml_v, cml_v, cll_v in rows:
    if is_section:
        # Section header spanning all columns
        merge_write(ws2, current_row, 1, current_row, 5,
            f"  {param}",
            fill=hex_fill(HEADER_BG),
            font=Font(name="Arial", bold=True, size=10, color="FFFFFF"),
            align=Alignment(horizontal="left", vertical="center"),
            border=thin_border()
        )
        ws2.row_dimensions[current_row].height = 20
    else:
        vals = [param, all_v, aml_v, cml_v, cll_v]
        bgs = [LABEL_BG, SEC_ALL, SEC_AML, SEC_CML, SEC_CLL]
        for col_idx, (val, bg) in enumerate(zip(vals, bgs), start=1):
            c = ws2.cell(row=current_row, column=col_idx)
            c.value = val
            c.fill = hex_fill(bg)
            if col_idx == 1:
                c.font = Font(name="Arial", bold=True, size=9, color="1A3C5E")
                c.alignment = Alignment(horizontal="left", vertical="center", wrap_text=True)
            else:
                # highlight key positive findings
                is_key = any(x in str(val) for x in ["POSITIVE", "hallmark", "pathognomonic", "MANDATORY", "MASSIVE", "✓", "HALLMARK"])
                c.font = Font(name="Arial", bold=is_key, size=9, color="1A1A1A")
                c.alignment = Alignment(horizontal="left", vertical="top", wrap_text=True)
            c.border = thin_border()
        # dynamic row height based on content
        max_lines = max(str(v).count("\n") + 1 for v in [all_v, aml_v, cml_v, cll_v, param])
        ws2.row_dimensions[current_row].height = max(18, min(15 * max_lines, 100))
    current_row += 1

# Footer
merge_write(ws2, current_row, 1, current_row, 5,
    "Source: Robbins & Cotran Pathologic Basis of Disease | Goldman-Cecil Medicine | Quick Compendium of Clinical Pathology  |  For MBBS/MD Exam Reference",
    fill=hex_fill("E8EDF2"),
    font=Font(name="Arial", italic=True, size=8, color="666666"),
    align=center()
)


# ══════════════════════════════════════════════════════════
# SHEET 3 – QUICK REFERENCE CARD
# ══════════════════════════════════════════════════════════
ws3 = wb.create_sheet("Quick Reference Card")
ws3.column_dimensions["A"].width = 20
ws3.column_dimensions["B"].width = 30
ws3.column_dimensions["C"].width = 30
ws3.column_dimensions["D"].width = 30
ws3.column_dimensions["E"].width = 30

merge_write(ws3, 1, 1, 2, 5,
    "⚡  LEUKEMIA QUICK REFERENCE CARD  —  HIGH-YIELD MBBS MNEMONICS & ONE-LINERS",
    fill=hex_fill(TITLE_BG),
    font=Font(name="Arial", bold=True, size=13, color="FFFFFF"),
    align=center()
)

quick_headers = ["LEUKEMIA", "ONE-LINER", "PATHOGNOMONIC SIGN", "DON'T MISS", "TREATMENT PEARL"]
for i, h in enumerate(quick_headers):
    c = ws3.cell(row=3, column=i+1)
    c.value = h
    c.fill = hex_fill(HEADER_BG)
    c.font = Font(name="Arial", bold=True, size=10, color="FFFFFF")
    c.alignment = center(wrap=True)
    c.border = thin_border()

quick_data = [
    (ALL_BG,  "ALL\n(Acute Lymphoblastic\nLeukemia)",
     "Most common childhood cancer. Lymphoblasts. TdT+. CALLA (CD10)+. t(12;21) = best; t(9;22) = worst. CNS prophylaxis mandatory.",
     "TdT POSITIVE\n(terminal deoxynucleotidyl\ntransferase)",
     "T-ALL → Anterior mediastinal mass in adolescent males!\nPh+ ALL → add TKI urgently",
     "Vincristine + Prednisolone\n+ L-Asparaginase\n+ Anthracycline (VPDL)\n+ Intrathecal MTX (CNS)"),

    (AML_BG,  "AML\n(Acute Myeloid\nLeukemia)",
     "Adults. Myeloblasts. Auer rods (MPO+). M3-APL = ATRA sensitive. '7+3' regimen (Cytarabine + Anthracycline). Watch for DIC in APL.",
     "AUER RODS\n(pink needle-like inclusions\nin myeloblasts; MPO+)",
     "M3-APL → DIC is life-threatening!\nStart ATRA immediately\n(do NOT wait for cytogenetics!)",
     "M3-APL: ATRA + Arsenic Trioxide\nOthers: Cytarabine (7 days)\n+ Idarubicin/Daunorubicin (3 days)"),

    (CML_BG,  "CML\n(Chronic Myeloid\nLeukemia)",
     "Philadelphia chromosome t(9;22) BCR-ABL1 p210. LOW LAP score. Massive splenomegaly. Imatinib (TKI) = treatment. 3 phases: Chronic → Accelerated → Blast Crisis.",
     "Philadelphia Chromosome\nt(9;22) BCR-ABL1\n+ LOW LAP score",
     "Blast crisis = transforms to AML (70%)\nor ALL (30%) → poor prognosis!\nBasophilia warns of crisis",
     "Imatinib (1st gen TKI) 400mg/day\nDasatinib / Nilotinib (2nd gen)\nPonatinib (T315I mutation)\nAlloSCT in blast crisis"),

    (CLL_BG,  "CLL\n(Chronic Lymphocytic\nLeukemia)",
     "Most common adult leukemia in West. Elderly. Mature B cells. CD5+/CD19+/CD23+. Smudge cells. Often asymptomatic. Richter transformation → DLBCL (5-10%). Watch & wait if stable.",
     "SMUDGE CELLS\n(fragile B lymphocytes\nrupture on smear)",
     "Hypogammaglobulinemia → recurrent infections\nAutoimmune hemolytic anemia (AIHA) in 10-15%\nRichter syndrome = sudden mass + B symptoms",
     "Watch & wait (asymptomatic)\nIbrutinib (BTK inhibitor)\nVenetoclax (BCL-2 inhibitor)\nRituximab (anti-CD20)\nFCR for fit patients"),
]

for i, (bg, name, oneliner, patho, miss, rx) in enumerate(quick_data):
    row = 4 + i
    data = [name, oneliner, patho, miss, rx]
    for col_idx, val in enumerate(data, start=1):
        c = ws3.cell(row=row, column=col_idx)
        c.value = val
        c.fill = hex_fill(bg if col_idx == 1 else "F8F9FA")
        if col_idx == 1:
            c.font = Font(name="Arial", bold=True, size=10, color="FFFFFF")
            c.alignment = center(wrap=True)
        else:
            c.font = Font(name="Arial", size=9, color="1A1A1A")
            c.alignment = Alignment(horizontal="left", vertical="top", wrap_text=True)
        c.border = thin_border()
    ws3.row_dimensions[row].height = 80

ws3.row_dimensions[3].height = 22

# ── MNEMONICS BOX ──
mnemo_row = 9
merge_write(ws3, mnemo_row, 1, mnemo_row, 5,
    "  MNEMONICS & HIGH-YIELD EXAM TIPS",
    fill=hex_fill(HEADER_BG),
    font=Font(name="Arial", bold=True, size=10, color="FFFFFF"),
    align=Alignment(horizontal="left", vertical="center")
)

mnemos = [
    ("TdT", "ONLY positive in ALL (lymphoblasts). Think: 'T for Terminal = T for ALL'"),
    ("Auer Rods", "ONLY in AML. 'Auer = AML'. Myeloperoxidase (MPO) stain positive. Pathognomonic."),
    ("Philadelphia Chromosome", "t(9;22) BCR-ABL1. ALWAYS in CML. Also in Ph+ ALL (poor prognosis). Think: 'Ph = Philly-Myeloid-Chronic'"),
    ("Smudge Cells", "ONLY in CLL. Fragile mature B cells rupture during smear preparation. Think: 'CLL cells are fragile old men'"),
    ("LAP Score", "LOW only in CML. Distinguishes from leukemoid reaction (high LAP). Think: 'CML Lowers Alkaline Phosphatase'"),
    ("CD5+ B cells", "ONLY seen in CLL (and Mantle Cell Lymphoma). CD5 is a T-cell marker aberrantly expressed in CLL."),
    ("Age Rule", "ALL = Children | AML = Middle-aged adults | CML = 40-60 yr | CLL = Elderly (>65)"),
    ("Splenomegaly", "MASSIVE → always CML. Moderate in all others."),
    ("M3-APL Emergency", "Start ATRA IMMEDIATELY for APL-M3 (do NOT wait). DIC can be fatal. t(15;17) PML-RARA."),
    ("CML Phases", "Chronic (blasts <10%) → Accelerated (blasts 10-19%) → Blast Crisis (blasts ≥20%, = acute leukemia)"),
]

for i, (key, tip) in enumerate(mnemos):
    row = mnemo_row + 1 + i
    c_key = ws3.cell(row=row, column=1)
    c_key.value = key
    c_key.fill = hex_fill("1A3C5E")
    c_key.font = Font(name="Arial", bold=True, size=9, color="FFFFFF")
    c_key.alignment = Alignment(horizontal="left", vertical="center", wrap_text=True)
    c_key.border = thin_border()

    merge_write(ws3, row, 2, row, 5,
        tip,
        fill=hex_fill("F0F4F8"),
        font=Font(name="Arial", size=9, color="1A1A1A"),
        align=Alignment(horizontal="left", vertical="center", wrap_text=True),
        border=thin_border()
    )
    ws3.row_dimensions[row].height = 22

# Footer
footer_row = mnemo_row + 1 + len(mnemos) + 1
merge_write(ws3, footer_row, 1, footer_row, 5,
    "Source: Robbins & Cotran Pathologic Basis of Disease | Goldman-Cecil Medicine | Quick Compendium of Clinical Pathology  |  © MBBS Medical Reference",
    fill=hex_fill("E8EDF2"),
    font=Font(name="Arial", italic=True, size=8, color="666666"),
    align=center()
)

# ─────────────────────────────────────────────────────────
# FREEZE PANES & PRINT SETTINGS
# ─────────────────────────────────────────────────────────
ws1.freeze_panes = "B3"
ws2.freeze_panes = "B4"
ws3.freeze_panes = "B4"

for ws in [ws1, ws2, ws3]:
    ws.sheet_view.showGridLines = True

# ─────────────────────────────────────────────────────────
# SAVE
# ─────────────────────────────────────────────────────────
output_path = "/tmp/workspace/leukemia-flowchart/Leukemia_Diagnostic_Flowchart_MBBS.xlsx"
wb.save(output_path)
print(f"Saved: {output_path}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/leukemia-flowchart/build_leukemia_excel.py'

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/leukemia-flowchart/build_leukemia_excel.py'