Hematologic Malignancies 101

from pptx import Presentation
from pptx.util import Inches, Pt, Emu
from pptx.dml.color import RGBColor
from pptx.enum.text import PP_ALIGN, MSO_ANCHOR
from pptx.oxml.ns import qn
from lxml import etree
from io import BytesIO

# ── Colour palette ─────────────────────────────────────────────────────────────
NAVY       = RGBColor(0x0D, 0x2D, 0x6B)   # deep navy  – headers / accents
TEAL       = RGBColor(0x00, 0x7B, 0x8A)   # teal       – sub-accents / bullets
LIGHT_BLUE = RGBColor(0xD6, 0xEA, 0xF8)   # sky blue   – content bg
WHITE      = RGBColor(0xFF, 0xFF, 0xFF)
DARK_GREY  = RGBColor(0x22, 0x22, 0x22)
MID_GREY   = RGBColor(0x55, 0x55, 0x55)
GOLD       = RGBColor(0xE6, 0xAC, 0x00)
RED_ACCENT = RGBColor(0xC0, 0x39, 0x2B)
GREEN      = RGBColor(0x1A, 0x7A, 0x3C)
AMBER      = RGBColor(0xD4, 0x6F, 0x00)

prs = Presentation()
prs.slide_width  = Inches(13.333)
prs.slide_height = Inches(7.5)
blank = prs.slide_layouts[6]

# ── Helper utilities ────────────────────────────────────────────────────────────
def add_rect(slide, x, y, w, h, fill_color=None, line_color=None, line_width=None):
    shape = slide.shapes.add_shape(1, Inches(x), Inches(y), Inches(w), Inches(h))
    if fill_color:
        shape.fill.solid()
        shape.fill.fore_color.rgb = fill_color
    else:
        shape.fill.background()
    if line_color:
        shape.line.color.rgb = line_color
        if line_width:
            shape.line.width = Pt(line_width)
    else:
        shape.line.fill.background()
    return shape

def add_tb(slide, x, y, w, h, text="", font_size=18, bold=False, color=DARK_GREY,
           align=PP_ALIGN.LEFT, wrap=True, italic=False):
    tb  = slide.shapes.add_textbox(Inches(x), Inches(y), Inches(w), Inches(h))
    tf  = tb.text_frame
    tf.word_wrap = wrap
    tf.margin_left = tf.margin_right = tf.margin_top = tf.margin_bottom = 0
    p   = tf.paragraphs[0]
    p.alignment = align
    if text:
        run = p.add_run()
        run.text = text
        run.font.size  = Pt(font_size)
        run.font.bold  = bold
        run.font.italic = italic
        run.font.color.rgb = color
        run.font.name  = "Calibri"
    return tf

def add_bullet_tb(slide, x, y, w, h, items, font_size=15, color=DARK_GREY,
                  bullet_color=TEAL, bold_first=False, line_spacing=1.15):
    tb  = slide.shapes.add_textbox(Inches(x), Inches(y), Inches(w), Inches(h))
    tf  = tb.text_frame
    tf.word_wrap = True
    tf.margin_left = tf.margin_right = tf.margin_top = tf.margin_bottom = 0
    for i, item in enumerate(items):
        p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
        p.space_before = Pt(2)
        run = p.add_run()
        run.text = f"  •  {item}"
        run.font.size  = Pt(font_size)
        run.font.name  = "Calibri"
        run.font.bold  = (bold_first and i == 0)
        run.font.color.rgb = color
    return tf

def header_bar(slide, title, subtitle=None):
    """Navy top bar with title + optional subtitle"""
    add_rect(slide, 0, 0, 13.333, 1.15, fill_color=NAVY)
    add_tb(slide, 0.4, 0.08, 12.5, 0.65, title, font_size=30, bold=True,
           color=WHITE, align=PP_ALIGN.LEFT)
    if subtitle:
        add_tb(slide, 0.4, 0.72, 12.5, 0.38, subtitle, font_size=14,
               color=RGBColor(0xAD, 0xD8, 0xE6), align=PP_ALIGN.LEFT, italic=True)

def footer_bar(slide, text="Plasma Cell Disorders | Hematology"):
    add_rect(slide, 0, 7.2, 13.333, 0.3, fill_color=NAVY)
    add_tb(slide, 0.3, 7.21, 12.5, 0.27, text, font_size=9,
           color=RGBColor(0xAD, 0xD8, 0xE6), align=PP_ALIGN.LEFT)

def divider(slide, y):
    add_rect(slide, 0.4, y, 12.5, 0.03, fill_color=TEAL)

def card(slide, x, y, w, h, bg=LIGHT_BLUE, border=TEAL, border_w=1.2):
    add_rect(slide, x, y, w, h, fill_color=bg, line_color=border, line_width=border_w)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 1 – TITLE
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=NAVY)
# diagonal accent strip
add_rect(s, 0, 5.8, 13.333, 1.7, fill_color=TEAL)
add_rect(s, 0, 5.6, 13.333, 0.25, fill_color=GOLD)

add_tb(s, 1, 1.2, 11, 1.0, "PLASMA CELL DISORDERS", font_size=42, bold=True,
       color=WHITE, align=PP_ALIGN.CENTER)
add_tb(s, 1, 2.3, 11, 0.5, "MGUS  ·  Smouldering Myeloma  ·  Multiple Myeloma",
       font_size=20, color=GOLD, align=PP_ALIGN.CENTER, italic=True)
divider_line = s.shapes.add_shape(1, Inches(3.5), Inches(2.95), Inches(6.3), Inches(0.04))
divider_line.fill.solid(); divider_line.fill.fore_color.rgb = GOLD
divider_line.line.fill.background()

add_tb(s, 1, 3.1, 11, 0.45,
       "Pathophysiology  ·  Clinical Features  ·  Investigations  ·  Management",
       font_size=16, color=RGBColor(0xAD, 0xD8, 0xE6), align=PP_ALIGN.CENTER)
add_tb(s, 1, 5.95, 11, 0.5, "Hematology Oncology Presentation", font_size=14,
       color=WHITE, align=PP_ALIGN.CENTER, italic=True)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 2 – OVERVIEW / SPECTRUM
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "The Plasma Cell Disorder Spectrum",
           "A continuum of clonal plasma cell proliferation")
footer_bar(s)

# Spectrum arrow bar
add_rect(s, 0.4, 1.4, 12.5, 0.55, fill_color=RGBColor(0xE8, 0xF4, 0xFD))
for x_pos, lbl, clr in [
    (0.5,  "MGUS",               GREEN),
    (3.8,  "Smouldering MM",     AMBER),
    (7.6,  "Multiple Myeloma",   RED_ACCENT),
]:
    add_rect(s, x_pos, 1.4, 3.0, 0.55, fill_color=clr)
    add_tb(s, x_pos, 1.4, 3.0, 0.55, lbl, font_size=16, bold=True,
           color=WHITE, align=PP_ALIGN.CENTER)
# arrow connectors text
add_tb(s, 3.5, 1.48, 0.6, 0.4, "➜", font_size=22, color=NAVY, align=PP_ALIGN.CENTER)
add_tb(s, 7.3, 1.48, 0.6, 0.4, "➜", font_size=22, color=NAVY, align=PP_ALIGN.CENTER)
add_tb(s, 10.6, 1.45, 2.3, 0.55, "~1%/yr risk", font_size=11,
       color=AMBER, align=PP_ALIGN.CENTER, italic=True)

# Three columns
cols = [
    (0.35, "MGUS", GREEN, [
        "M-protein < 3 g/dL",
        "Clonal BM plasma cells < 10%",
        "No CRAB criteria",
        "No end-organ damage",
        "~1% per year risk of progression",
        "Prevalence: ~3% in adults >50 yrs",
    ]),
    (4.55, "Smouldering MM", AMBER, [
        "M-protein ≥ 3 g/dL  OR",
        "Clonal BM plasma cells 10–60%",
        "No CRAB / myeloma defining events",
        "2-year risk: ~10% in standard risk",
        "High-risk: up to 50% in 2 years",
        "Active surveillance mandatory",
    ]),
    (8.75, "Multiple Myeloma", RED_ACCENT, [
        "Clonal BM plasma cells ≥ 10%",
        "CRAB criteria present  OR",
        "Any myeloma-defining event",
        "Biopsy-proven plasmacytoma",
        "Requires immediate treatment",
        "Median survival: 5–7 years",
    ]),
]
for cx, ctitle, cclr, citems in cols:
    card(s, cx, 2.1, 4.05, 0.45, bg=cclr, border=cclr)
    add_tb(s, cx+0.05, 2.1, 3.95, 0.45, ctitle, font_size=14, bold=True,
           color=WHITE, align=PP_ALIGN.CENTER)
    card(s, cx, 2.55, 4.05, 4.3, bg=RGBColor(0xF5, 0xF9, 0xFF), border=cclr, border_w=1.5)
    add_bullet_tb(s, cx+0.1, 2.62, 3.85, 4.1, citems, font_size=13, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 3 – PATHOPHYSIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Pathophysiology of Multiple Myeloma",
           "Clonal plasma cell expansion driving multi-organ dysfunction")
footer_bar(s)

# Left column – molecular basis
card(s, 0.35, 1.3, 5.8, 5.65, bg=RGBColor(0xEA, 0xF4, 0xFF), border=NAVY, border_w=1.5)
add_tb(s, 0.45, 1.35, 5.6, 0.4, "Molecular Basis", font_size=15, bold=True, color=NAVY)
divider(s, 1.77)
mol_items = [
    "HSC → B-cell → germinal centre → plasma cell",
    "Initiating hit: Ig gene translocations (t(4;14), t(14;16), t(11;14))",
    "Secondary hits: MYC dysregulation, RAS/MAPK mutations, del(17p) TP53",
    "RANKL upregulation → osteoclast activation → bone destruction",
    "IL-6 (myeloma growth factor) secreted by stromal cells",
    "DKK1 inhibits Wnt → suppresses osteoblasts",
    "Excess M-protein → renal tubular injury (cast nephropathy)",
    "BM infiltration → cytopenias (anaemia, thrombocytopenia)",
    "Suppressed normal Ig → hypogammaglobulinaemia → infections",
]
add_bullet_tb(s, 0.45, 1.85, 5.6, 5.1, mol_items, font_size=12.5, color=DARK_GREY)

# Right column – bone marrow microenvironment
card(s, 6.5, 1.3, 6.48, 5.65, bg=RGBColor(0xFD, 0xF0, 0xF0), border=RED_ACCENT, border_w=1.5)
add_tb(s, 6.6, 1.35, 6.3, 0.4, "The Myeloma Bone Marrow Niche", font_size=15,
       bold=True, color=RED_ACCENT)
divider(s, 1.77)
bm_items = [
    "Myeloma cells interact with BM stromal cells via adhesion molecules (VLA-4, VCAM-1)",
    "Stromal contact triggers NF-κB, PI3K/AKT, RAS/MAPK → survival & drug resistance",
    "Angiogenesis increased (VEGF secretion)",
    "Immunosuppressive milieu: Tregs, MDSCs, PD-L1 expression",
    "Osteolytic cycle: M-cells → ↑RANKL + ↓OPG → osteoclasts → bone destruction",
    "Calcium released from bone → hypercalcaemia",
    "Bence Jones proteins (free light chains) filtered → tubular damage → AKI/CKD",
    "Amyloid deposits possible (AL amyloidosis) with systemic infiltration",
]
add_bullet_tb(s, 6.6, 1.85, 6.2, 5.1, bm_items, font_size=12.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 4 – CLINICAL FEATURES + CRAB
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Clinical Features — CRAB Criteria & Myeloma-Defining Events",
           "End-organ damage requiring initiation of therapy")
footer_bar(s)

# CRAB boxes
crab_data = [
    ("C", "HyperCalcaemia",  RED_ACCENT,
     ["Serum Ca > 0.25 mmol/L above ULN  or  > 2.75 mmol/L",
      "Mechanism: RANKL-mediated osteoclast activation",
      "Features: Nausea, polyuria, polydipsia, confusion",
      "'Bones, Groans, Moans, Psychic Overtones'"]),
    ("R", "Renal Failure",   AMBER,
     ["Creatinine > 177 µmol/L  or  CrCl < 40 mL/min",
      "Mechanisms: Cast nephropathy (commonest), amyloid,",
      "  hypercalcaemia, hyperuricaemia, drug toxicity",
      "Light chains precipitate with Tamm-Horsfall protein"]),
    ("A", "Anaemia",         TEAL,
     ["Hb < 100 g/L  or  > 20 g/L below LLN",
      "Mechanism: BM infiltration + cytokine suppression",
      "Normocytic normochromic; Rouleaux on blood film",
      "Raised ESR due to M-protein"]),
    ("B", "Bone Lesions",    NAVY,
     ["Lytic bone lesions on skeletal survey / WB-MRI",
      "Mechanism: Osteoclast activation, osteoblast suppression",
      "Sites: Skull, spine, ribs, pelvis, proximal long bones",
      "Vertebral fractures → back pain, cord compression"]),
]
box_w = 3.1
for i, (letter, title, clr, pts) in enumerate(crab_data):
    xpos = 0.25 + i * 3.27
    # Coloured letter box
    add_rect(s, xpos, 1.3, 0.7, 0.7, fill_color=clr)
    add_tb(s, xpos, 1.3, 0.7, 0.7, letter, font_size=32, bold=True,
           color=WHITE, align=PP_ALIGN.CENTER)
    add_rect(s, xpos+0.7, 1.3, 2.5, 0.7, fill_color=clr)
    add_tb(s, xpos+0.72, 1.32, 2.4, 0.65, title, font_size=14, bold=True,
           color=WHITE, align=PP_ALIGN.LEFT)
    card(s, xpos, 2.0, 3.2, 3.2, bg=RGBColor(0xF7, 0xF9, 0xFF), border=clr, border_w=1.2)
    add_bullet_tb(s, xpos+0.1, 2.08, 3.0, 3.0, pts, font_size=11.5, color=DARK_GREY)

# SLiM criteria bar
add_rect(s, 0.25, 5.3, 12.83, 1.65, fill_color=RGBColor(0xF0, 0xF0, 0xFF))
add_tb(s, 0.4, 5.32, 12.5, 0.35,
       "SLiM — Myeloma-Defining Events (trigger treatment even without CRAB)",
       font_size=13, bold=True, color=NAVY)
slim_items = [
    "S – Sixty percent (≥60%) clonal plasma cells in bone marrow",
    "Li – Light chain ratio: involved/uninvolved FLC ratio ≥ 100",
    "M – MRI: >1 focal lesion (≥5 mm) on whole-body MRI",
]
add_bullet_tb(s, 0.4, 5.7, 12.5, 1.1, slim_items, font_size=12.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 5 – CLINICAL FEATURES: RECURRENT INFECTIONS, BONE PAIN, RENAL
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Key Clinical Features in Detail",
           "Recurrent Infections · Bone Pain · Renal Impairment")
footer_bar(s)

panels = [
    (0.3, "🦠  Recurrent Infections", TEAL,
     ["Hypogammaglobulinaemia: clonal Ig suppresses normal B-cell function",
      "CD4+ T-cell and NK-cell dysfunction",
      "Neutropenia from BM infiltration ± chemotherapy",
      "Organisms: Streptococcus pneumoniae, H. influenzae (encapsulated bacteria)",
      "Viral reactivation: Herpes zoster, CMV in transplant patients",
      "Prophylaxis: IVIG replacement, cotrimoxazole (PCP), antiviral cover",
      "Pneumococcal & flu vaccines recommended at diagnosis",
      "Common presentation: recurrent pneumonia, sinusitis, UTI",
     ]),
    (4.6, "🦴  Bone Pain", RED_ACCENT,
     ["Presenting symptom in ~70% of patients",
      "Mechanism: Osteoclast activation (RANKL/OPG imbalance) + loss of osteoblast function",
      "Sites: Back (vertebrae), ribs, skull, sternum, long bones",
      "Pathological fractures: vertebral collapse → acute severe back pain",
      "Spinal cord compression: emergency! (5%) → paraplegia if untreated",
      "'Punched-out' lytic lesions on plain X-ray (skeletal survey)",
      "Whole-body low-dose CT or WB-MRI preferred over plain films",
      "Bisphosphonates (zoledronic acid) or denosumab for bone protection",
     ]),
    (8.9, "🩺  Renal Impairment", AMBER,
     ["Present in ~50% at diagnosis; 20% require dialysis",
      "Cast nephropathy (myeloma kidney): FLC + Tamm-Horsfall protein → tubular obstruction",
      "Direct tubular toxicity of free light chains (proximal tubular injury)",
      "Hypercalcaemia → nephrocalcinosis + volume depletion → AKI",
      "AL amyloidosis: glomerular deposits → nephrotic syndrome",
      "NSAID use + dehydration worsens renal function",
      "Reversible with hydration + prompt myeloma treatment",
      "Daratumumab-based regimens preferred in renal failure",
     ]),
]
for px, ptitle, pclr, pitems in panels:
    card(s, px, 1.3, 4.1, 5.7, bg=RGBColor(0xF5, 0xF8, 0xFF), border=pclr, border_w=2.0)
    add_rect(s, px, 1.3, 4.1, 0.52, fill_color=pclr)
    add_tb(s, px+0.1, 1.3, 3.9, 0.52, ptitle, font_size=14, bold=True,
           color=WHITE, align=PP_ALIGN.LEFT)
    add_bullet_tb(s, px+0.12, 1.9, 3.86, 5.0, pitems, font_size=11.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 6 – INVESTIGATIONS
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Investigations",
           "Establishing diagnosis, staging & risk stratification")
footer_bar(s)

inv_cols = [
    (0.3, "Blood Tests", NAVY, [
        "FBC: normocytic anaemia, Rouleaux on film, raised ESR",
        "U&E / LFTs: renal impairment, raised Ca²⁺, LDH",
        "Serum protein electrophoresis (SPEP): M-protein band",
        "Serum immunofixation: identifies Ig class (IgG, IgA, light chain)",
        "Serum free light chain (FLC) assay: κ/λ ratio",
        "β₂-microglobulin (ISS staging), albumin (ISS staging)",
        "LDH: correlates with tumour burden",
        "Uric acid, coagulation screen",
    ]),
    (4.55, "Urine Tests", TEAL, [
        "24-hour urine: protein quantification",
        "Urine electrophoresis (UPEP): Bence Jones protein (monoclonal FLC)",
        "Urine immunofixation: confirms light chain type",
        "Urine FLC: serial monitoring of response",
        " ",
        "Bone Marrow",
        "Trephine biopsy + aspirate: ≥10% clonal plasma cells",
        "Flow cytometry: CD138+, CD38+, CD19-, CD56+",
        "FISH / cytogenetics: del(17p), t(4;14), t(14;16), t(11;14), del(1p), gain 1q",
    ]),
    (8.8, "Imaging", RED_ACCENT, [
        "Whole-body low-dose CT (WBLDCT): first-line imaging",
        "  → Lytic lesions, fractures, soft tissue masses",
        "Whole-body MRI (WB-MRI): bone marrow involvement,",
        "  sensitivity for smouldering MM / cord compression",
        "PET-CT: disease extent, treatment response, extramedullary",
        "Skeletal survey (plain X-ray): historic; less sensitive",
        "Echocardiogram: if AL amyloidosis suspected",
        "Bone density (DEXA): baseline for bisphosphonate monitoring",
    ]),
]
for cx, ctitle, cclr, citems in inv_cols:
    add_rect(s, cx, 1.3, 4.15, 0.48, fill_color=cclr)
    add_tb(s, cx+0.1, 1.3, 3.95, 0.48, ctitle, font_size=15, bold=True,
           color=WHITE, align=PP_ALIGN.LEFT)
    card(s, cx, 1.78, 4.15, 5.12, bg=RGBColor(0xF5, 0xF9, 0xFF), border=cclr, border_w=1.2)
    add_bullet_tb(s, cx+0.12, 1.88, 3.92, 4.9, citems, font_size=12, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 7 – STAGING
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Staging & Risk Stratification",
           "International Staging System (ISS) and Revised ISS (R-ISS)")
footer_bar(s)

# ISS table
add_tb(s, 0.4, 1.28, 6.0, 0.38, "International Staging System (ISS)",
       font_size=14, bold=True, color=NAVY)
iss_rows = [
    ("Stage", "Criteria", "Median OS", NAVY, WHITE),
    ("I",   "β₂M < 3.5 mg/L  AND  Albumin ≥ 35 g/L",    "62 months", GREEN,       WHITE),
    ("II",  "Neither Stage I nor Stage III",               "44 months", AMBER,       WHITE),
    ("III", "β₂M ≥ 5.5 mg/L",                             "29 months", RED_ACCENT,  WHITE),
]
row_h = 0.56
for ri, (s1, s2, s3, rbg, rtxt) in enumerate(iss_rows):
    y = 1.68 + ri * row_h
    add_rect(s, 0.4, y, 0.9, row_h, fill_color=rbg, line_color=WHITE, line_width=0.5)
    add_rect(s, 1.3, y, 4.5, row_h, fill_color=rbg, line_color=WHITE, line_width=0.5)
    add_rect(s, 5.8, y, 1.8, row_h, fill_color=rbg, line_color=WHITE, line_width=0.5)
    add_tb(s, 0.42, y+0.06, 0.86, row_h-0.1, s1, font_size=13 if ri>0 else 12,
           bold=(ri==0), color=rtxt, align=PP_ALIGN.CENTER)
    add_tb(s, 1.32, y+0.06, 4.45, row_h-0.1, s2, font_size=12 if ri>0 else 12,
           bold=(ri==0), color=rtxt)
    add_tb(s, 5.82, y+0.06, 1.75, row_h-0.1, s3, font_size=12 if ri>0 else 12,
           bold=(ri==0), color=rtxt, align=PP_ALIGN.CENTER)

# R-ISS
add_tb(s, 7.9, 1.28, 5.0, 0.38, "Revised ISS (R-ISS)",
       font_size=14, bold=True, color=NAVY)
r_iss = [
    ("R-ISS I",   "ISS I + standard cytogenetics + LDH ≤ ULN",   "Not reached", GREEN),
    ("R-ISS II",  "Not R-ISS I or III",                            "83 months",  AMBER),
    ("R-ISS III", "ISS III + high-risk cytogenetics OR LDH > ULN", "43 months",  RED_ACCENT),
]
for ri2, (st, crit, os, clr) in enumerate(r_iss):
    y2 = 1.68 + ri2 * 1.0
    add_rect(s, 7.9, y2, 5.0, 0.95, fill_color=RGBColor(0xF5, 0xF9, 0xFF),
             line_color=clr, line_width=1.5)
    add_rect(s, 7.9, y2, 2.0, 0.95, fill_color=clr)
    add_tb(s, 7.92, y2+0.12, 1.96, 0.7, st, font_size=13, bold=True,
           color=WHITE, align=PP_ALIGN.CENTER)
    add_tb(s, 9.93, y2+0.04, 2.9, 0.45, crit, font_size=11, color=DARK_GREY, wrap=True)
    add_tb(s, 9.93, y2+0.5, 2.9, 0.38, f"Median OS: {os}", font_size=11,
           color=MID_GREY, italic=True)

# High-risk cytogenetics
add_rect(s, 7.9, 4.75, 5.0, 2.1, fill_color=RGBColor(0xFF, 0xF0, 0xF0),
         line_color=RED_ACCENT, line_width=1.5)
add_tb(s, 8.0, 4.78, 4.8, 0.38, "High-Risk Cytogenetics", font_size=13,
       bold=True, color=RED_ACCENT)
hrc = ["del(17p) / TP53 mutation", "t(4;14) – FGFR3/MMSET",
       "t(14;16) – MAF", "t(14;20) – MAFB", "Gain 1q / del 1p"]
add_bullet_tb(s, 8.0, 5.18, 4.8, 1.5, hrc, font_size=12, color=DARK_GREY)

# Amyloid / other note
add_rect(s, 0.4, 4.75, 7.1, 2.1, fill_color=RGBColor(0xF0, 0xF5, 0xFF),
         line_color=NAVY, line_width=1.2)
add_tb(s, 0.55, 4.78, 6.8, 0.38, "Myeloma Defining Events (MDEs) — SLiM Criteria",
       font_size=13, bold=True, color=NAVY)
slim2 = [
    "≥60% clonal plasma cells in BM (regardless of M-protein level)",
    "Serum FLC ratio ≥100 (involved ÷ uninvolved)",
    ">1 focal lesion on WB-MRI (≥5 mm each)",
    "Any of the above → diagnosis of MM + treatment required",
]
add_bullet_tb(s, 0.55, 5.18, 6.8, 1.5, slim2, font_size=12, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 8 – MANAGEMENT OVERVIEW
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Management Overview",
           "MGUS · Smouldering MM · Active Myeloma")
footer_bar(s)

mgmt_cols = [
    (0.3, "MGUS", GREEN, [
        "NO treatment required",
        "Baseline investigations to confirm no end-organ damage",
        "Monitor M-protein & FLC ratio every 6–12 months",
        "Repeat BM biopsy only if progression suspected",
        "Patient education: symptoms to report",
        "Lifestyle: stay hydrated, avoid nephrotoxins",
        "Annual review lifelong",
        "Risk stratification guides monitoring intensity:",
        "  – Low risk: M-protein <1.5 g/dL, IgG, normal FLC → q12m",
        "  – High risk: IgA/IgM, M-protein >1.5 g/dL → q6m",
    ]),
    (4.6, "Smouldering MM", AMBER, [
        "Standard risk: close observation (no treatment)",
        "High-risk SMM: lenalidomide ± dexamethasone considered",
        "QUIREDEX / E3A06 trials support early Rx for high-risk",
        "Daratumumab monotherapy (AQUILA trial) approved high-risk",
        "Definition of high-risk SMM (Mayo 2018):",
        "  – BM plasma cells ≥20%",
        "  – M-protein ≥2 g/dL",
        "  – FLC ratio ≥20",
        "Monitoring: CBC, chemistry, SPEP q3–4 months",
        "WB-MRI at baseline and q12–24 months",
    ]),
    (8.9, "Active MM — Goals", RED_ACCENT, [
        "Reduce tumour burden & achieve deep remission",
        "Prevent/treat complications (bone, renal, infection)",
        "Assess transplant eligibility first",
        "Response categories (IMWG):",
        "  – sCR → CR → VGPR → PR → SD → PD",
        "MRD negativity (10⁻⁵ by NGF/NGS) = best predictor",
        "Novel targets: BCMA, GPRC5D, FcRH5",
        "CAR-T cell therapy: ide-cel, cilta-cel (relapsed/refractory)",
        "Bispecifics: teclistamab, elranatamab",
        "Allogeneic SCT: investigational",
    ]),
]
for cx, ctitle, cclr, citems in mgmt_cols:
    add_rect(s, cx, 1.3, 4.1, 0.48, fill_color=cclr)
    add_tb(s, cx+0.1, 1.3, 3.9, 0.48, ctitle, font_size=15, bold=True,
           color=WHITE, align=PP_ALIGN.LEFT)
    card(s, cx, 1.78, 4.1, 5.12, bg=RGBColor(0xF5, 0xF9, 0xFF), border=cclr, border_w=1.2)
    add_bullet_tb(s, cx+0.12, 1.88, 3.86, 4.9, citems, font_size=11.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 9 – INDUCTION & TRANSPLANT
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Active Myeloma — Induction Therapy & Stem Cell Transplant",
           "Treatment stratified by transplant eligibility")
footer_bar(s)

# Transplant eligible
card(s, 0.3, 1.3, 6.1, 5.7, bg=RGBColor(0xE8, 0xF8, 0xF5), border=GREEN, border_w=2.0)
add_rect(s, 0.3, 1.3, 6.1, 0.5, fill_color=GREEN)
add_tb(s, 0.4, 1.3, 5.9, 0.5, "Transplant-Eligible (<65–70 yrs, good PS)",
       font_size=14, bold=True, color=WHITE)
te_items = [
    "Induction (3–4 cycles): VRd (Bortezomib + Lenalidomide + Dexamethasone)",
    "  OR DRd (Daratumumab + Lenalidomide + Dexamethasone) — preferred in high risk",
    "  OR VCd (Bortezomib + Cyclophosphamide + Dexamethasone)",
    "",
    "Stem Cell Collection:",
    "  G-CSF ± plerixafor for mobilisation",
    "  Collect peripheral blood stem cells (minimum 2 × 10⁶ CD34+/kg)",
    "",
    "High-Dose Chemotherapy: Melphalan 200 mg/m²",
    "",
    "Autologous SCT — improves PFS and OS vs. conventional chemo",
    "",
    "Consolidation: additional VRd cycles (optional)",
    "Maintenance: Lenalidomide until progression (standard)",
    "  Bortezomib added for t(4;14) or del(17p) (high-risk)",
    "",
    "Tandem transplant: considered for high-risk disease",
]
add_bullet_tb(s, 0.4, 1.85, 5.9, 5.1, te_items, font_size=11.5, color=DARK_GREY)

# Transplant ineligible
card(s, 6.8, 1.3, 6.2, 5.7, bg=RGBColor(0xFD, 0xF5, 0xE6), border=AMBER, border_w=2.0)
add_rect(s, 6.8, 1.3, 6.2, 0.5, fill_color=AMBER)
add_tb(s, 6.9, 1.3, 6.0, 0.5, "Transplant-Ineligible (>70 yrs or significant comorbidity)",
       font_size=14, bold=True, color=WHITE)
ti_items = [
    "Preferred regimen: DRd (Daratumumab + Lenalidomide + Dex)",
    "  – MAIA trial: significant OS benefit vs. Rd alone",
    "",
    "Alternative: DVd (Daratumumab + Bortezomib + Melphalan + Pred)",
    "  – ALCYONE trial: OS benefit in elderly patients",
    "",
    "VMP (Bortezomib + Melphalan + Prednisone): older standard",
    "Rd (Lenalidomide + low-dose Dexamethasone): well-tolerated",
    "",
    "Dose modifications required for:",
    "  – Renal impairment (lenalidomide dose reduce per CrCl)",
    "  – Peripheral neuropathy (bortezomib → switch to ixazomib)",
    "",
    "Maintenance: Lenalidomide until progression",
    "  Daratumumab SC maintenance also an option",
    "",
    "Supportive: bisphosphonate (zoledronic acid q4w x 2 yrs)",
    "DVT prophylaxis with lenalidomide (aspirin or LMWH)",
]
add_bullet_tb(s, 6.9, 1.85, 5.9, 5.1, ti_items, font_size=11.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 10 – SUPPORTIVE CARE
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Supportive Care & Complication Management",
           "Treating the consequences of myeloma")
footer_bar(s)

supp = [
    (0.3,  1.3, "Bone Disease",      NAVY, [
        "Bisphosphonates: Zoledronic acid 4 mg IV q4w (2 yrs min)",
        "Denosumab (anti-RANKL): preferred in renal impairment",
        "Kyphoplasty / vertebroplasty for painful vertebral fractures",
        "Radiotherapy (8–10 Gy) for localised painful bone lesions",
        "Orthopaedic surgery for impending pathological fractures",
        "Dental review before bisphosphonate (osteonecrosis risk)",
    ]),
    (0.3,  4.55, "Renal Support",     TEAL, [
        "IV hydration: maintain UO >3 L/day",
        "Avoid NSAIDs, contrast, nephrotoxins",
        "Treat hypercalcaemia (IVF + furosemide ± bisphosphonate)",
        "Haemodialysis if severe AKI / chronic renal failure",
        "Bortezomib-based regimens: safe in renal failure",
        "Lenalidomide: dose-reduce per CrCl",
    ]),
    (6.8,  1.3, "Infection Prevention", TEAL, [
        "Pneumococcal & influenza vaccination",
        "Cotrimoxazole (PCP prophylaxis during high-dose steroids)",
        "Aciclovir / valaciclovir (VZV prophylaxis with bortezomib)",
        "IVIG replacement if severe hypogammaglobulinaemia",
        "G-CSF for neutropenia (chemotherapy-induced)",
        "Central venous catheter care protocols",
    ]),
    (6.8,  4.55, "Anaemia & Haematological", RED_ACCENT, [
        "Blood transfusion for symptomatic anaemia",
        "Erythropoiesis-stimulating agents (ESAs) in selected patients",
        "Thromboprophylaxis: aspirin/LMWH with IMiD-based therapy",
        "Treat hypercalcaemia promptly (bisphosphonate IV + IVF)",
        "Allopurinol for tumour lysis syndrome risk",
        "Plasmapheresis for hyperviscosity (rare, Waldenstrom's more)",
    ]),
]
for sx, sy, stitle, sclr, sitems in supp:
    card(s, sx, sy, 6.1, 3.05, bg=RGBColor(0xF5, 0xF8, 0xFF), border=sclr, border_w=1.5)
    add_rect(s, sx, sy, 6.1, 0.4, fill_color=sclr)
    add_tb(s, sx+0.1, sy, 5.9, 0.4, stitle, font_size=13, bold=True, color=WHITE)
    add_bullet_tb(s, sx+0.12, sy+0.45, 5.86, 2.5, sitems, font_size=11.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 11 – RELAPSED / REFRACTORY + NOVEL THERAPIES
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=WHITE)
header_bar(s, "Relapsed & Refractory Myeloma — Novel Therapies",
           "Emerging agents transforming outcomes")
footer_bar(s)

therapy_classes = [
    (0.3,  1.3, "IMiDs",                    TEAL,       ["Thalidomide (historic)", "Lenalidomide (Revlimid)", "Pomalidomide (Imnovid)", "Mechanism: Cereblon-mediated degradation of IKZF1/3"]),
    (3.55, 1.3, "Proteasome Inhibitors",    NAVY,       ["Bortezomib (IV/SC) – 1st gen", "Carfilzomib (Kyprolis) – 2nd gen", "Ixazomib (Ninlaro) – oral", "Mechanism: Inhibit 26S proteasome → UPR → apoptosis"]),
    (6.8,  1.3, "Monoclonal Antibodies",    RED_ACCENT, ["Daratumumab (anti-CD38)", "Isatuximab (anti-CD38)", "Elotuzumab (anti-SLAMF7)", "Mechanism: ADCC, CDC, phagocytosis"]),
    (10.05,1.3, "Alkylating / Steroids",    MID_GREY,   ["Melphalan (HD conditioning)", "Cyclophosphamide (VCD)", "Dexamethasone (backbone)", "Bendamustine (salvage)"]),
    (0.3,  4.3, "CAR-T Cell Therapy",       RGBColor(0x6A,0x0D,0xAD), ["Ide-cel (idecabtagene vicleucei)", "Cilta-cel (ciltacabtagene autoleucel)", "Target: BCMA (B-cell maturation antigen)", "Deep MRD-negative responses; FDA approved RRMM"]),
    (3.55, 4.3, "Bispecific Antibodies",    RGBColor(0x00,0x66,0x00), ["Teclistamab (BCMA × CD3)", "Elranatamab (BCMA × CD3)", "Talquetamab (GPRC5D × CD3)", "Linvoseltamab (BCMA × CD3)"]),
    (6.8,  4.3, "Exportin-1 Inhibitor",     AMBER,      ["Selinexor (Xpovio)", "Blocks nuclear export of TSPs", "Used in penta-refractory disease", "Oral agent, combined with dexamethasone"]),
    (10.05,4.3, "Antibody-Drug Conjugates", RGBColor(0x8B,0x00,0x00), ["Belantamab mafodotin (BCMA-ADC)", "Target: BCMA + MMAF cytotoxin", "Corneal microdeposits (keratopathy)", "Re-evaluated post KarMMa-3 trial data"]),
]
for tx, ty, ttitle, tclr, titems in therapy_classes:
    card(s, tx, ty, 2.9, 2.85, bg=RGBColor(0xF5, 0xF8, 0xFF), border=tclr, border_w=1.5)
    add_rect(s, tx, ty, 2.9, 0.4, fill_color=tclr)
    add_tb(s, tx+0.08, ty, 2.74, 0.4, ttitle, font_size=11.5, bold=True, color=WHITE)
    add_bullet_tb(s, tx+0.1, ty+0.45, 2.7, 2.3, titems, font_size=10.5, color=DARK_GREY)

# ══════════════════════════════════════════════════════════════════════════════
#  SLIDE 12 – SUMMARY / KEY TAKE-AWAYS
# ══════════════════════════════════════════════════════════════════════════════
s = prs.slides.add_slide(blank)
add_rect(s, 0, 0, 13.333, 7.5, fill_color=NAVY)
add_rect(s, 0, 1.1, 13.333, 6.4, fill_color=WHITE)
header_bar(s, "Summary & Key Take-Aways", "Plasma Cell Disorders at a Glance")
footer_bar(s)

takeaways = [
    ("1", "Spectrum",      "MGUS → Smouldering MM → Active MM represents a continuous biological spectrum of clonal plasma cell evolution."),
    ("2", "Pathophysiology","M-protein, osteoclast activation, marrow infiltration and immune suppression drive all the key features."),
    ("3", "Diagnose MM",   "≥10% clonal BM plasma cells + CRAB criteria OR SLiM myeloma-defining events."),
    ("4", "Work-up",       "SPEP + immunofixation + FLC assay + BM biopsy + FISH + WB-CT/MRI. β₂M + albumin for ISS staging."),
    ("5", "Treatment",     "Triplet induction (VRd or DRd) → ASCT in eligible → maintenance lenalidomide. Daratumumab backbone for most."),
    ("6", "Complications", "Manage bone disease (bisphosphonates), renal failure (hydration, avoid nephrotoxins), infections (prophylaxis)."),
    ("7", "Novel Rx",      "CAR-T (ide-cel, cilta-cel) and bispecifics (teclistamab) are transforming outcomes in RRMM."),
    ("8", "Prognosis",     "R-ISS III: ~43-month median OS. MRD-negativity is the best surrogate for prolonged survival."),
]
cols_per_row = 4
row_h2 = 2.55
for i, (num, title, body) in enumerate(takeaways):
    col = i % cols_per_row
    row = i // cols_per_row
    bx = 0.3 + col * 3.23
    by = 1.3 + row * row_h2
    add_rect(s, bx, by, 3.0, row_h2 - 0.12,
             fill_color=RGBColor(0xF0, 0xF5, 0xFF), line_color=TEAL, line_width=1.0)
    add_rect(s, bx, by, 0.5, row_h2 - 0.12, fill_color=TEAL)
    add_tb(s, bx, by + 0.4, 0.5, 0.7, num, font_size=18, bold=True,
           color=WHITE, align=PP_ALIGN.CENTER)
    add_tb(s, bx+0.55, by+0.06, 2.4, 0.38, title, font_size=12, bold=True, color=NAVY)
    add_tb(s, bx+0.55, by+0.45, 2.4, 1.9, body, font_size=10.5, color=DARK_GREY, wrap=True)

# ── Save ───────────────────────────────────────────────────────────────────────
out = "/tmp/workspace/plasma-cell-disorders/Plasma_Cell_Disorders.pptx"
buf = BytesIO()
prs.save(buf)
with open(out, "wb") as f:
    f.write(buf.getvalue())
print(f"Saved: {out}")